Clin Radiol ; 56 — Brain health and self-care of Dieease phenotype with gene transfer requires liver- and muscle-targeted GDE expression. Viser G, Rake JP, Fernandes, et al. The prevention of HCA and HCC were described by Lee et al.

Management of glycogen storage disease -

Because of the abundance of adenomas, biopsy is not an option. There is no effective biomarker because α-fetoprotein and carcinoembryonic antigen levels are often normal even in the setting of HCC. No good imaging tool separates HCA from HCC. Until recently, the genetic makeup of the adenomas from patients with GSD I was not known.

However, Kishnani et al. Although loss of 6q without gain of 6p was identified in two non-GSD I HCA general population HCAs in this study, and simultaneous gain of 6p and loss of 6q has been reported in two general population HCAs in a previous report, the significance of loss of 6q for HCA development in the general population was inconclusive because the aberration was just one of multiple chromosomal aberrations in these cases.

It is speculated that GSD I HCA with simultaneous gain of 6p and loss of 6q could confer high risk for malignant transformation, implicating genes on chromosome 6 in the transformation of HCA to HCC.

Patients with these high-risk aberrations may be good candidates for LT until we have a better understanding of the pathogenesis and other therapeutic targets. These findings also suggest that good metabolic control alone may be insufficient to prevent the development of HCA in some patients with GSD I.

In the general population, HCAs regress in some patients after the cessation of oral contraceptives. In GSD I, there is some evidence that metabolic control may be a modifier of adenoma formation and progression, but there are cases in which adenomas occur despite good metabolic control.

Whereas most investigators agree that HCAs in GSD Ia patients should be observed for signs of malignancy, the management of concerning lesions is not established. Liver imaging is routinely performed in individuals with GSD I. With increasing age, computed tomography or magnetic resonance imaging scanning using i.

contrast should be considered to look for evidence of increasing lesion size, poorly defined margins, or spontaneous hemorrhage. contrast to minimize the number of missed lesions is recommended. It is also known that α-fetoprotein and carcinoembryonic antigen levels do not predict the presence of HCAs or malignant transformation 24 , in patients with GSD I see next section.

Initially, the management of liver adenomas in the GSD I population should be conservative Box 3. An approach of watchful waiting may be used. There are reports of the use of percutaneous ethanol injection as the initial treatment of enlarging liver adenomas.

Resection of HCAs suspected of being malignant is an effective intermediate step in the prevention of HCC in GSD Ia patients. As such, adenoma resection may be used as the initial management of lesions suspicious for malignancy in GSD I.

A study by Reddy et al. In this study it was noted that GSD Ia patients present with a greater burden of adenomatous disease and shorter progression-free survival after resection than the general population. This experience of HCA resection in GSD Ia patients demonstrates that partial hepatectomy is feasible in these patients and is an effective intermediate step in the prevention of HCC until definitive treatment such as a LT.

Because of the low numbers, the true risks of partial hepatectomy particular to this population have not been explored. Liver replacement is the ultimate therapy for hepatic metabolic disease. It should be considered for patients with multifocal, growing lesions that do not regress with improved dietary regimens and who do not have evidence of distant metastatic disease.

The first reported LT for GSD I was performed in ref However, there are several obstacles to LT in GSD Ia patients. These include uncertainties regarding timing of transplantation, limited organ availability, prospects of worsening renal function with immunosuppression, and fears of poor patient compliance with immunosuppressive medication given a history of faulty adherence to a strict dietary regimen.

This score is calculated using a logarithmic assessment of three objective and reproducible variables, namely total serum bilirubin and creatinine concentrations, and the international normalized ratio. The score may range from as low as 6 to a high of A MELD score of 15—17 is significant in that this is the point at which the mortality risk associated with liver disease and its complications is equivalent to the 1-year mortality associated with complications arising from LT.

In GSD I, because the hepatic abnormalities are the result of a single-gene, cell-autonomous defect, there is no possibility of recurrence of primary liver disease within the transplanted allograft. The most common indication for liver transplantation in GSD I has been hepatic adenomatous disease for removal of potentially premalignant lesions.

Other indications have included growth failure and poor metabolic control. Transplantation should be reserved for patients who have not had success with medical management, have a history of recurrent adenomas despite liver resection, have a rapid increase in the size and number of liver adenomas, and are at high risk for liver cancer.

Although the survival rate after transplantation has improved over the past 20 years, complications in the postoperative course remain. Chronic renal failure is a well-documented complication of liver transplantation in GSD Ia, and some patients with GSD Ia have progressed to renal failure within a few years of transplantation.

Alternatively, a primary GSD-related nephrotoxic effect may be present because of the untreated condition in the kidney. Postoperative pulmonary hypertension has also been documented in a small number of patients after transplantation. Although hypoglycemia similarly abates when liver transplantation is performed in GSD Ib, the neutropenia, neutrophil dysfunction, and Crohn disease—like inflammatory bowel disease are variably affected by liver transplantation.

G-CSF is still often needed to treat the neutropenia associated with GSD Ib despite normalization of the metabolic profile after liver transplantation because neutropenia is primarily attributable to an intrinsic defect in the neutrophils of GSD Ib patients and is not corrected by LT.

Renal manifestations of GSD I appear early in childhood and often go undetected without specific diagnostic evaluation. Glycogen deposition occurs in the kidneys, which typically are large on renal imaging; however, nephromegaly is not sufficient to be readily detected on physical examination.

As a result of both the metabolic perturbations that arise and the glycogen accumulation with GSD I, there can be not only proximal and distal renal tubular dysfunction but also progressive glomerular injury that can result in functional renal impairment and even end-stage renal disease requiring renal replacement therapy.

Specific interventions aimed at ameliorating or trying to prevent the progression of these renal consequences of GSD I are best commenced early after their presentation to have the best opportunity to alter the course of renal injury.

The proximal tubule is the site of a great deal of energy expenditure and G6Pase activity is normally highest. With proximal tubular dysfunction, wasting of bicarbonate, phosphate, glucose, and amino acids can be seen. In GSD I, proximal tubular dysfunction has been ascribed to glycogen accumulation in proximal tubular cells or inability to produce glucose for metabolic needs.

In children with poorly controlled GSD I, there tends to be more documentation of aminoaciduria and phosphaturia because these children have such low serum glucose and bicarbonate levels that little tubular reabsorption is required. The other proximal tubular defects improve with effective therapy such as the provision of CS and, as a result, tend not to be seen in most patients receiving treatment to maintain glucose levels.

Along the proximal tubule, there is also sodium-linked reabsorption of calcium and the organic acids such as citrate that can freely cross the glomerular filtration barrier. The citrate that remains in the urine plays an important role in enhancing the ionic strength of the urine, essentially chelating urinary calcium and helping to prevent its precipitation and the development of nephrolithiasis or nephrocalcinosis.

As a result, individuals with low urinary citrate levels are more predisposed to urinary tract calcifications, and such urinary tract calcifications can increase the chances of urinary tract infection or mediate renal parenchymal damage with loss of renal functional reserve.

With GSD I, instead of the usual increasing urinary excretion of citrate with ongoing maturity, there is an actual decrease in citrate excretion that accelerates during adolescence and early adulthood.

Glycogen deposition in the proximal tubule does reduce proximal tubular calcium reabsorption and is the likely mechanism for altered urinary calcium levels in GSD I. Hypercalciuria is widespread in prepubertal children with GSD I, and the likelihood for nephrolithiasis and nephrocalcinosis increases with ongoing significant elevation in urinary calcium levels.

Oral citrate supplementation will augment citrate excretion, favorably altering the urinary milieu to decrease the chances of urinary calcium precipitation and, as a result, is likely very beneficial in GSD I patients with low urinary citrate levels Box 4. In individuals with normal renal function, potassium citrate is preferred over sodium citrate because higher sodium intake is linked to greater urinary calcium excretion.

It also can result in systemic hypertension. In older children and adults, potassium citrate tablets at a dose of 10 mEq three times per day can also be commenced and the dose adjusted as needed.

Because the effects of citrate supplementation wane over time, multiple daily doses spread over the waking hours are preferred to maximize the proportion of the day with improved urinary citrate levels.

Citrate use should be monitored because it can cause hypertension and life-threatening hyperkalemia in the setting of renal impairment. Patients should also be monitored for sodium levels. With hypercalciuria, thiazide diuretics can also be provided as a way to enhance renal reabsorption of filtered calcium and decrease urinary calcium excretion.

Especially in GSD I individuals with known urinary tract calcification and ongoing hypercalciuria, thiazide diuretic therapy can be considered. Chlorothiazide is used in young children who require liquid preparations; tablets of hydrochlorothiazide are recommended for older children and adults.

The efficacy of therapy can be gauged by interval urinary calcium-to-creatinine ratios. This ability to decrease urinary calcium excretion is unique to thiazide diuretics, unlike other classes of diuretics that tend to increase urinary calcium excretion. Other nonspecific measures to reduce urinary calcium deposition, such as optimizing hydration, maintaining a no-added salt diet, or supplementing magnesium intake, can also be considered on an individual basis as well.

GSD I mediates hemodynamic and structural changes in the kidney that can lead to the development of glomerular injury. The exact mechanisms by which these changes occur are not well understood, but activation of the renin—angiotensin system, prolonged oxidative stress, and profibrotic cytokines such as transforming growth factor-β have all been implicated, as well as alterations in renal tubular epithelial cell energy stores related to G6Pase defects.

These changes in GFR may not be readily detected because they result in serum creatinine levels that are often reported as normal.

With hyperfiltration, enhanced glomerular blood flow and intraglomerular pressure occur. As glomeruli become obsolete, fibrosis replaces surface area that previously allowed filtration. Histologically, this injury appears as focal and segmental sclerosis, with a subset of glomeruli demonstrating limited scarring.

As more and more glomeruli are lost to scarring, the overall GFR decreases and there is then an accelerated rate of obsolescence in these remnant glomeruli, creating even more stimuli for further glomerular injury.

Over time, microalbuminuria has a tendency to progress to frank proteinuria with urinary protein-to-creatinine ratios exceeding 0. Chronic proteinuria is thought to exacerbate glomerular injury through induction of chemokines and inflammatory pathways.

In GSD I, the development of pathologic proteinuria may be inevitable. In GSD I, this initial period of hyperfiltration that leads to microalbuminuria and frank proteinuria does seem to then progress to widespread glomerular scarring and eventual renal dysfunction.

Most renal biopsy samples from GSD I patients with frank proteinuria or any decrease in GFR demonstrate focal and segmental sclerosis as the histologic change that precedes the loss of renal function and progression to end-stage renal disease.

There have been some data to suggest that metabolic control in GSD I may affect the progression of renal injury. For many years, angiotensin blockade has been used to blunt proteinuria and slow loss of GFR in patients with renal diseases such as diabetes mellitus, in which there is similar hyperfiltration injury.

In cases in which there is a need for further angiotensin blockade, use of both an ACE and an ARB can prove synergistic to reduce proteinuria, with no increased rate of hyperkalemia or drug-related renal insufficiency.

Although not yet tested in any systematic fashion in GSD I, the role of initiating angiotensin blockade with the early onset of persistent microalbuminuria seems to be a potential strategy to try to slow the factors that cause accelerated glomerular obsolescence and that ultimately lead to microalbuminuria, proteinuria, and renal insufficiency.

Typical measures to maintain GSD metabolic control are beneficial to general renal health because they help prevent acidosis and limit hyperuricemia and hyperlipidemia.

Chronic acidosis can predispose to higher urinary calcium excretion and decreased urinary citrate, both problems that already exist in GSD I. Hyperuricemia and hyperlipidemia by themselves have both been implicated in causing or accelerating renal injury.

In patients receiving effective dietary therapy for their GSD I, it is unlikely that there will be diffuse proximal tubular dysfunction. There should be periodic assessment of serum electrolytes, calcium, and phosphate as well as interval measurement of blood urea nitrogen and creatinine levels.

GFR should be estimated from the serum creatinine using a validated formula such as the Bedside Schwartz Equation in children or the Modification of Diet in Renal Disease Equation for adults.

Screening urinalysis should be performed at intervals on all GSD I patients. The presence of hematuria determined by dipstick should lead to assessment of urinary calcium excretion and ultrasound imaging of the urinary tract for calcifications.

Even in the absence of hematuria, renal ultrasound should be performed at intervals to assess kidney size and to assess for evolving nephrocalcinosis or nephrolithiasis.

Especially for purposes of screening or for routine follow-up, ultrasound is preferred to other imaging techniques. Despite good metabolic control, hypocitraturia and hypercalciuria may be common in GSD I and, as a result, urine should be assessed at regular intervals for calcium and citrate excretion even if urinalysis is benign.

Spot samples are adequate and easier and quicker to collect than are those of timed urine collection. With hypocitraturia, citrate supplementation should be considered, especially if there is concomitant hypercalciuria or a history of nephrolithiasis or nephrocalcinosis. With hypercalciuria, there needs to be ongoing good hydration and consideration of thiazide therapy to reduce urinary calcium levels, especially in individuals with known or recurrent urinary tract calcifications.

Urine should also be assessed for microalbuminuria and proteinuria. With a negative screening urinalysis for proteins, urine albuminuria should be quantified by spot albumin-to-creatinine ratio.

Dipstick-positive proteinuria should be quantified by urinary protein-to-creatinine ratio. Positive results should be confirmed using a first morning void sample to rule out any orthostatic component.

Persistent microalbuminuria or frank proteinuria warrants initiation of angiotensin blockade despite patients being normotensive. Medications should be adjusted to try to blunt the proteinuria to levels that are normal or as near normal as possible as tolerated without causing postural hypotension or hyperkalemia.

Attempts should be made to maintain angiotensin blockade chronically, and medication sequelae should be treated in some fashion so that the angiotensin blockade can be maintained or a different type of angiotensin blockade ACE vs.

ARB should be attempted. Because chronic hypertension accelerates renal injury, blood pressure should be maintained in a normal range for adults and at less than the 90th percentile for age, gender, and height for children. If antihypertensive therapy needs to be started, angiotensin blockade with ACE or ARB should be considered as first-line therapy if not already instituted for other reasons.

Loop diuretics should be avoided because of the risk of hypercalciuria. With renal insufficiency, there is decreased production of erythropoietin EPO by the kidney and anemia may develop.

Concomitant clinical factors in GSD patients such as chronic metabolic acidosis, iron deficiency, and bleeding diathesis may potentiate or exacerbate this anemia. In children and adolescents with chronic kidney disease, anemia is linked to impairments in cognitive and developmental gains as well as increased hospitalization rates.

With adults, there are fewer data to support a specific hemoglobin level under which EPO should be started. As a result, EPO therapy is initiated if there is any evolving symptomatic anemia to prevent the need for blood transfusion. Because iron deficiency anemia is common in GSD I, it is prudent to screen both children and adults with chronic renal failure for iron deficiency anemia and replace iron as needed before starting EPO therapy.

Long-term exposure to nephrotoxic medications should also be avoided. This includes use of nonsteroidal anti-inflammatory drugs such as ibuprofen and is especially important if there is any reduction in GFR or if patients have a bleeding diathesis.

Metabolic derangements from ongoing chronic renal insufficiency may exacerbate some of the issues that arise from GSD, making renal transplantation a more attractive therapy.

In this case the option of both liver and kidney transplant may be considered. Hematologic aspects in GSD I include risk for anemia, bleeding diathesis, and neutropenia in GSD Ib. Anemia is a significant long-term morbidity in individuals with GSD I. In , Talente et al.

The report was based on an observational study of 32 subjects. Anemia in the pediatric population was recognized in ref. The cause of anemia in GSD I is multifactorial—the restricted nature of the diet, chronic lactic acidosis, renal involvement, bleeding diathesis, chronic nature of the illness, suboptimal metabolic control, 40 hepatic adenomas, 29 and irritable bowel disease in GSD Ib are all contributing factors.

In one study it was noted that patients with hemoglobin concentrations 2 SDs below the mean for their age had higher mean daily lactate concentrations as compared with the nonanemic population 3. An association between severe anemia and large hepatic adenomas was identified as well.

Many patients with GSD I have iron deficiency anemia. In some, it is an iron refractory anemia attributable to aberrant expression of hepcidin. It is secreted in the bloodstream and is the key regulator of iron in the body, controlling iron absorption across the enterocyte, as well as macrophage recycling of iron.

In the presence of hepatic adenomas, there are increased hepcidin levels. The inability of hepcidin to be downregulated in the setting of anemia causes abnormal iron absorption and iron deficiency. Intravenous iron infusions can partially overcome the resistance to iron therapy, but, because of an inhibition of macrophage recycling of iron, a good response is typically not seen.

The restricted nature of the diet, with a focus on maintaining normoglycemia, often results in nutritional deficiencies see Nutrition section including poor intake of iron, vitamin B12, and folic acid. Progression of kidney disease is another risk factor for anemia, and some patients require supplementation with EPO to maintain hemoglobin levels.

The causes of anemia in GSD Ib are similar to those of anemia in GSD Ia, as was noted in five subjects studied by Talente et al. Numerous case reports documented the presence of anemia in this population, but studies of the pathophysiology of this complication were lacking.

Interleukin 6—a marker of inflammation known to upregulate hepcidin expression, which is increased during inflammatory bowel disease exacerbations—is the likely cause of low hemoglobin concentrations and another cause for the anemia observed in patients with GSD Ib.

A larger study involving subjects with GSD I at two large GSD centers has shed more light on the causes of anemia in GSD I. Mild anemia is common in the pediatric population because of iron deficiency and dietary restrictions.

As previously stated, overall, pediatric patients with anemia have worse metabolic control, but the anemia is responsive to improved therapy and iron supplementation.

By contrast, anemia in adulthood is associated with hepatic adenoma formation, particularly in people with more severe anemia. The finding that all subjects who had resection of the dominant hepatic adenoma experienced resolution of their anemia supports the proposed pathophysiology of hepcidin-induced anemia.

In contrast to the GSD Ia population, there was no association between anemia and metabolic control or hepatic adenomas in either children or adults with GSD Ib; however, a strong association with systemic inflammation was documented. In GSD I, a coagulation defect attributed to acquired platelet dysfunction with prolonged bleeding times, decreased platelet adhesiveness, and abnormal aggregation has been described Box 5.

Bleeding manifestations include epistaxis, easy bruising, menorrhagia, 45 and excessive bleeding during surgical procedures. Although dietary intervention can ameliorate the bleeding diathesis, the exact etiology of the bleeding diathesis remains unclear.

More than one study, with limited numbers of patients, showed that infusions of glucose and total parenteral nutrition corrected the bleeding time and in vitro platelet function in patients with GSD I, suggesting that coagulation defects were secondary to metabolic abnormalities.

These agents could be utilized in patients with GSD I when clinically indicated, but use of deamino d -arginine vasopressin in GSD I must be performed with caution because of the risk of fluid overload and hyponatremia in the setting of i. glucose administration.

In addition, the use of a fibrinolytic inhibitor, such as ɛ-aminocaproic acid Amicar , can be used as an adjunctive medication if there is mucosal-associated bleeding. For more severe mucosal-associated bleeding, an i.

If the i. The use of Amicar is contraindicated in individuals with disseminated intravascular coagulation and if activated prothrombin complex concentrate FEIBA has been used. Caution must be taken to ensure that there is no genitourinary tract bleeding, because inhibition of fibrinolysis can lead to an obstructive nephropathy.

Neutropenia and recurrent infections are common manifestations of GSD Ib. Neutropenia persists throughout childhood with little change in the neutrophil levels.

It is unclear if neutrophil function is normal in this setting. Adult patients also have severe neutropenia and recurrent infections. The patterns of infections vary from patient to patient, but there is no clear genotype—phenotype relationship.

Neutropenia and the susceptibility to infections are now attributed to specific abnormalities in neutrophil production and function. Mutations in glucose 6-phosphate transporter G6PT cause apoptosis of developing neutrophils, ineffective neutrophil production, and neutropenia.

Monocyte functions are also abnormal, probably contributing to the formation of granulomas and chronic inflammatory responses. It is also important to note that some patients with GSD Ia have also been known to develop neutropenia. Individuals with GSD Ia who are homozygous for the mutation p.

GlyArg were reported to have a GSD Ib—like phenotype with neutropenia. G-CSF has been used for treating neutropenia and preventing infections in patients with GSD Ib since refs. This cytokine stimulates and accelerates neutrophil production by the bone marrow, releases neutrophils from the bone marrow, prolongs the survival of the cells, and enhances their metabolic burst.

Administration of G-CSF increases blood neutrophil counts to normal or above normal levels, usually within a few hours. In a review of 18 European patients given either glycosylated or nonglycosylated G-CSF median age: 8 years; treated for up to 7 years , there was a positive clinical response both in the severity of infections and in the manifestations of inflammatory bowel disease in all patients.

Almost all reports on GSD Ib indicate that G-CSF increases blood neutrophil levels, decreases the occurrence of fevers and infections, and improves enterocolitis.

Before G-CSF treatment, median ANC for this group was 0. Treatment can be performed daily, on alternate days, or on a Monday—Wednesday—Friday schedule with similar benefits DC Dale, personal communication , but some children require daily therapy to avoid infections.

G-CSF should be administered subcutaneously starting at 1. The G-CSF dose should be increased in a stepwise manner at approximately 2-week intervals until the target ANC of more than to up to 1. The ANC for these patients is not pushed to higher levels because G-CSF appears to increase the spleen size in GSD Ib patients.

Blood count should be monitored several times per year. The lowest effective G-CSF dose should be used to avoid splenomegaly, hypersplenism, hepatomegaly, and bone pain. With use of G-CSF, occurrences of infections were greatly reduced and inflammatory bowel disease also improved in most, but not all, patients.

In more than patient-years of observations, the Severe Chronic Neutropenia International Registry has recorded three deaths in GSD Ib patients, sepsis, 1; after liver and hematopoietic transplant, 1; hepatomegaly and neutropenia, 1.

Side effects of treatment with G-CSF in the GSD Ib population were reported by the European Study on Glycogen Storage Disease Type I.

This complication did regress with reduced treatment. There are known cases in which the splenomegaly did not improve with reduction of the dose and splenectomy was required. Increase in spleen size and the need to reduce G-CSF dose can usually be determined by physical examination and confirmed by ultrasound when necessary.

In addition, this group reported two patients that have been on G-CSF and developed acute myelogenous leukemia. Based on available data, the risk of acute myelogenous leukemia is very low. However, all patients should be observed, with serial blood counts monitored approximately quarterly for development of loss of response to G-CSF, presence of myeloblasts in the blood, evidence of hypersplenism, new patterns of bone pain, or any other changes that might suggest a change in hematological disease or development of a myeloid malignancy.

In contrast to the hypertrophic cardiomyopathy of GSD II Pompe disease or GSD III, the heart itself is not primarily affected by GSD I. The most common cardiovascular abnormality in patients with GSD I is systemic hypertension Box 6. This is reviewed in the Nephrology section of this article.

There are conflicting data about this question, and two small series examining clinical surrogates of early atherosclerosis found no evidence to suggest early atherosclerosis.

One of the most ominous, yet rare, potential complications of GSD I is the occurrence of pulmonary arterial hypertension PAH. PAH may coexist with numerous systemic illnesses such as rheumatologic diseases, portal hypertension, infections such as HIV , and exposure to toxins anorexigens.

PAH is also known to be a complication of several other conditions, such as hypoxic lung disease, thromboembolic disease, pulmonary venous hypertension secondary to left-sided heart disease, and congenital heart disease with left-to-right shunting through the lungs.

Finally, it may occur in isolation as primary PAH. To date, nine GSD I patients with PAH have been reported.

This suggests that the GSD I patient with a coexisting condition that may also predispose a patient to development of PAH is at the highest risk for this complication. In all the cases of GSD I with PAH described in the literature, the diagnosis of PAH was not made until it was quite advanced, and in seven of nine patients PAH led to their deaths.

Recently, oral medications for PAH, such as sildenafil, have been shown to be effective treatments. GSD I patients with this serious complication have a better chance of longer survival if PAH is diagnosed at an earlier stage and medical treatment is initiated promptly.

Management recommendations for cardiovascular manifestations of GSD I include screening to detect systemic or pulmonary hypertension at early stages when these conditions are most amenable to treatment.

Because systemic hypertension in children is only rarely associated with clinical symptoms such as headaches or vision changes beginning in infancy, accurate measurements of systemic blood pressure should be obtained at all clinic visits.

Any elevated blood pressure measurements should be carefully followed up to confirm the diagnosis of hypertension. It is important to note that age-appropriate and gender-appropriate norms for blood pressure should be applied when reporting it. Good metabolic control is the best management option for maintaining serum lipid levels as close to normal as possible, thereby reducing the risk of acute pancreatitis and long-term development of atherosclerosis.

Management of hyperlipidemia with medications usually does not begin until the patient is at least 10 years old. Screening for pulmonary hypertension by periodic echocardiography with attention to estimating right-ventricular pressure by tricuspid regurgitation jet is indicated because PAH is unlikely to have clinical features that would be apparent on physical examination or with simple testing such as electrocardiogram until the PAH is well advanced.

Obtaining the tricuspid regurgitation jet by echocardiogram is the best method to periodically screen for elevated right-side heart pressures. Because most of the patients with PAH also had poor metabolic control, achieving good metabolic control may prevent PAH.

If PAH is detected, pursuing effective treatment methods such as treatment with Bosentan and Sildenafil in consultation with a physician experienced in managing PAH is recommended. The primary-care physician should take care of the regular physical examinations and immunizations, as well as any intercurrent medical problem not related to the GSD.

Other available immunizations, such as those for seasonal influenza, hepatitis B, and pneumococcal infections polyvalent after 2 years of age , should be offered because they can prevent the hypoglycemia caused by the gastrointestinal manifestations associated with the disease processes.

Hepatitis C status should be monitored in patients at risk. Because patients with GSD I may receive several medications, it is always recommended to check for potential interactions with the physician or pharmacy when a new medication is prescribed.

Drugs that can potentially cause hypoglycemia should be avoided. These include β-blockers, quinidine, sulfonamides Bactrim , pentamidine, and haloperidol, as well as some over-the-counter medications.

Antidepressant agents should be used with caution because they can affect glucose regulation hypoglycemia or hyperglycemia. Insulin and insulin secretagogues sulfonylureas should be used with caution. The use of growth hormone should clearly be limited to only those who are proven to have a growth hormone deficiency and, in this situation, close monitoring for liver adenomas and metabolic disturbances is critical.

The use of aspirin, nonsteroidal anti-inflammatory drugs, and other medications that reduce or affect platelet function should be avoided. Hypoglycemia risks should be checked before starting medications.

Due consideration should be given to medications that have a high sodium or potassium content; the latter is especially important in the setting of renal failure. All patients should be encouraged to participate in age-appropriate physical activities.

However, contact or competitive sports should be avoided because of the risk of liver injury, unless proper protection is used. Patients should avoid alcohol intake as it may predispose them to hypoglycemia.

Good hygiene and frequent hand-washing precautions are advised, especially for patients with neutropenia. As a general rule, patients should avoid unnecessary contact with sick people, especially during the winter season.

Good dental hygiene and frequent monitoring of dental health are advised for all patients, but it is particularly important in patients with GSD Ib, who have a tendency to develop chronic gingivitis.

During intercurrent illnesses, early evaluation and treatment are encouraged to prevent complications, especially when infectious processes are suspected in patients with neutropenia. In such cases more frequent monitoring of BG and additional doses of CS may be indicated.

glucose treatment. The emergency letter should be reviewed annually and updated as needed. Patients should wear a medical alert identification. A variety of types are offered by pharmacies and websites:.

Necklaces and bracelets with engraved patient name, diagnosis, and emergency contact information. org offers a sponsored membership program that provides bracelets with an engraved toll-free telephone number and patient ID number.

Metabolic derangement caused by fasting and infections are a common cause of morbidity in patients with GSD I, even with current treatments. In addition, some illnesses causing anorexia and vomiting interrupt oral or nasogastric feedings. Patients and their parents should be educated regarding the symptoms of hypoglycemia and metabolic decompensation.

They should be taught to respond to minor ailments by giving frequent oral or NG glucose-containing fluids, and they should be educated regarding the need for emergency care if oral feeds are not tolerated. Of course, due consideration of fluid volume is given in the setting of renal failure.

Intravenous solutions containing lactate are contraindicated and should be avoided. Patients with GSD I cannot tolerate typical periods of fasting before procedures.

Progressive metabolic acidosis and cardiac dysrhythmia leading to cardiac arrest during surgery have been reported. Recommendations have been published as a guide for perioperative management. supply of glucose can be provided. The i. BG, electrolyte, and lactic acid levels should be monitored.

Although administration of dextrose-containing fluids at lower rates can result in normalization of BG, higher doses of glucose are needed to keep the patient anabolic and prevent lactic acidosis.

fluids should continue until oral feeding is re-established. Once the patient is taking oral feedings, the dextrose infusion should be slowly weaned over several hours. Caution should be used when prescribing hormonal birth control; estrogen is known to contribute to development of both benign and malignant hepatocellular tumors Box 9.

Females with GSD I are known to have polycystic ovaries from a young age. Menorrhagia appears to be a problem in females of reproductive age with GSD I. Management of females with GSD I should include a multidisciplinary approach including the expertise of a gynecologist familiar with GSD I.

With significant strides in management of GSD I, patients are surviving into adulthood and pregnancies are now becoming common. Successful pregnancies have been documented in women with GSD types Ia and Ib. Ideally, it is prudent to plan the pregnancy ahead of time so that metabolic parameters may be monitored and normalized in preparation for pregnancy.

A prepregnancy consultation should be conducted during which adherence to a safe diet routine to avoid low BG, accompanied by frequent BG monitoring, should be emphasized. Medications such as ACE inhibitors, allopurinol, and lipid-lowering drugs must be discontinued because they are known to cause fetal anomalies.

A baseline ultrasound of the kidneys and liver to monitor for hepatic adenomas should be performed before the patient becomes pregnant. Laboratory tests such as a lipid profile, serum uric acid test, liver function test, complete blood count, and urine protein test should be performed.

Good metabolic control will help normalize most of these parameters if abnormal. In addition, in patients with GSD Ib, conception at a time when inflammatory bowel disease is quiescent may make flare-ups during pregnancy less likely. The high estrogenic state in pregnancy has been reported to cause an increase in adenoma formation.

Increased proteinuria may be noted. Risk of stone formation is typically higher in GSD Ia than in GSD Ib, 40 but renal calcification was noted in two of three pregnant patients with GSD Ib in one case series.

Neutropenia and Crohn disease—like enterocolitis are problems unique to GSD Ib. Low neutrophil counts can lead to infectious complications. G-CSF is classified by the US Food and Drug Administration as a pregnancy class C drug. There are no recommendations for G-CSF use during pregnancy.

There are published reports in the literature of normal pregnancy outcomes after G-CSF use. Management of Crohn disease—like enterocolitis can be problematic in pregnancy because most medications used for treatment are not approved for use during pregnancy.

The risk to the fetus from active enterocolitis has to be considered in comparison with the risk from the medications themselves during decision making regarding management.

BG levels should be monitored throughout the process to maintain euglycemia. Transient hypoglycemia has been observed in some neonates. Neonates have been noted to have normal growth and development. There is no contraindication to breastfeeding.

Increased metabolic demands will occur while breastfeeding. It has been observed that not all mothers may be successful at breastfeeding. The website provides descriptions of the various types of GSD and a listserv, a mechanism for people with all forms of GSD to connect via the Internet.

The association also holds a medical conference each year for individuals with GSD and their families. Similar to that for other inborn errors of metabolism, genetic counseling should be offered to all parents of children with GSD I and to adults affected with the condition Box GSD I is an autosomal recessive condition.

De novo mutation rates are expected to be infrequent, and parents of an affected individual are assumed to be carriers. DNA mutation analysis is necessary for the identification of additional family members in the extended family who may be carriers.

Targeted mutation analysis based on ethnic background is available for both the G6PC and SLC37A4 genes. Generally, full sequence analysis is recommended, starting with GSD Ia and then GSD Ib, if clinical suspicion is present.

Large deletions and duplications cannot be detected by sequence analysis. Identification of carrier status in the general population is limited and not routinely offered; however, mutation analysis to further refine the risk of having a child with GSD I can be offered to those at risk e.

Prenatal diagnostic testing is typically performed by mutation analysis either on cultured chorionic villus samples or on amniocytes, ideally of the probands of previously identified mutations. When the mutations segregating in the family are known, molecular testing is the gold standard.

Prenatal genetic diagnosis is also an option for families with GSD I if the mutations have been identified. Acute and chronic complications occur in GSD Ia despite adherence to dietary therapy, including growth retardation, hepatomegaly, intermittent hypoglycemia, lactic acidemia, hyperlipidemia, gout related to hyperuricemia, proteinuria, nephrolithiasis, and progressive nephropathy.

Modified CS shows promise for improving dietary therapy because a single dose at bedtime prevented hypoglycemia more effectively throughout the night in comparison with uncooked CS. Perhaps one of the most concerning complications of GSD I is the frequent occurrence of hepatic adenomas in adult patients, which are accompanied by a significant risk for malignant transformation to HCC.

The mechanism for tumorigenesis remains to be elucidated in GSD Ia, although it could include chronic inflammation. Progressive nephropathy is associated with proteinuria in adult patients. The overexpression of angiotensinogen suggests that suppression of the renin—angiotensin system might be effective in GSD Ia.

Microalbuminuria has been effectively treated with low doses of ACE inhibitors such as captopril and lisinopril.

In a study of 95 patients with GSD I, a significant and progressive decrease of glomerular hyperfiltration was noted in patients treated with ACE inhibitors. Hyperlipidemia in GSD Ia can be managed with lipid-lowering drugs such as 3-hydroxymethyl-glutaryl-CoA reductase inhibitors and fibrates.

The potential benefit of 3-hydroxymethyl-glutaryl-CoA reductase inhibitors was emphasized by a study that showed increased triglyceride synthesis in GSD Ia patients compared with normal controls. Hyperuricemia in GSD I can improve with good metabolic control; however, in some situations, hyperuricemia persists and can result in gouty attacks, gouty tophi, and kidney stones.

Use of agents, such as Allopurinol and Febuxostat, have been used to lower uric acid levels. Newer agents, such as pegloticase, have been used in situations where the use of other agents has failed.

Colchicine has been used with success in the acute setting of gouty attacks. At this time, there is no consensus as when to treat hyperuricemia with medications. The development of new therapy for GSD Ia, such as gene therapy or cell therapy, might prevent long-term complications that arise due to recurrent hypoglycemia and related biochemical abnormalities.

Pilot studies of hepatocyte transplantation have demonstrated persistence of donor cells, although the long-term efficacy of this approach remains to be demonstrated , Efficacy from liver-targeted gene therapy in GSD Ia might be expected, given the experience with human patients after liver transplantation.

Furthermore, complications of GSD Ib were incompletely reversed in experiments with an AAV vector encoding G6PT, and longer-term surviving mice developed hepatocellular carcinoma related to inadequate correction.

The duration of efficacy from AAV vectors has been limited, because the AAV vector genomes remain largely episomal and are lost after cell division. A double-stranded AAV vector transduced the liver and kidneys with higher efficiency when pseudotyped as AAV9 rather than the AAV8 vector used for initial experiments; however, G6Pase expression from these vectors gradually waned between 7 and 12 months of age.

The loss of G6Pase could be countered by readministration of an AAV vector of a new serotype to avoid antibodies formed in response to the initial AAV vector treatment.

Despite these apparent limitations of gene therapy in GSD I, the development of AAV vector—mediated gene therapy will continue based on the success of early-stage clinical trials of gene therapy in hemophilia.

Gierke EV. Hepato-nephro-megalia-glycogenica Glykogenspeicherkrankheit der Leber und Nieren. Beitr Pathol Anat ; 82 — Google Scholar. Cori GT, Cori CF. Glucosephosphatase of the liver in glycogen storage disease. J Biol Chem ; — Article CAS PubMed Google Scholar. Narisawa K, Igarashi Y, Otomo H, Tada K.

A new variant of glycogen storage disease type I probably due to a defect in the glucosephosphate transport system. Biochem Biophys Res Commun ; 83 — Lei KJ, Shelly LL, Pan CJ, Sidbury JB, Chou JY. Mutations in the glucosephosphatase gene that cause glycogen storage disease type 1a. Science ; — Treatment GSDI is treated with a special diet in order to maintain normal glucose levels, prevent hypoglycemia and maximize growth and development.

Frequent small servings of carbohydrates must be maintained during the day and night throughout the life. Calcium, vitamin D and iron supplements maybe recommended to avoid deficits. Frequent feedings of uncooked cornstarch are used to maintain and improve blood levels of glucose.

Allopurinol, a drug capable of reducing the level of uric acid in the blood, may be useful to control the symptoms of gout-like arthritis during the adolescent years.

Human granulocyte colony stimulating factor GCSF may be used to treat recurrent infections in GSD type Ib patients.

Liver tumors adenomas can be treated with minor surgery or a procedure in which adenomas are ablated using heat and current radiofrequency ablation.

Individuals with GSDI should be monitored at least annually with kidney and liver ultrasound and routine blood work specifically used for monitoring GSD patients. Information on current clinical trials is posted on the Internet at www.

All studies receiving U. government funding, and some supported by private industry, are posted on this government web site. For information about clinical trials being conducted at the National Institutes of Health NIH in Bethesda, MD, contact the NIH Patient Recruitment Office:.

Tollfree: TTY: Email: prpl cc. For information about clinical trials sponsored by private sources, contact: www. TEXTBOOKS Chen YT, Bali DS. Prenatal Diagnosis of Disorders of Carbohydrate Metabolism. In: Milunsky A, Milunsky J, eds.

Genetic disorders and the fetus — diagnosis, prevention, and treatment. West Sussex, UK: Wiley-Blackwell; Chen Y. Glycogen storage disease and other inherited disorders of carbohydrate metabolism.

In: Kasper DL, Braunwald E, Fauci A, et al. New York, NY: McGraw-Hill; Weinstein DA, Koeberl DD, Wolfsdorf JI. Type I Glycogen Storage Disease. In: NORD Guide to Rare Disorders. Philadelphia, PA: Lippincott, Williams and Wilkins; JOURNAL ARTICLES Chou JY, Jun HS, Mansfield BC.

J Inherit Metab Dis. doi: Epub Oct 7. PubMed PMID: Kishnani PS, Austin SL, Abdenur JE, Arn P, Bali DS, Boney A, Chung WK, Dagli AI, Dale D, Koeberl D, Somers MJ, Wechsler SB, Weinstein DA, Wolfsdorf JI, Watson MS; American College of Medical Genetics and Genomics. Genet Med.

Austin SL, El-Gharbawy AH, Kasturi VG, James A, Kishnani PS. Menorrhagia in patients with type I glycogen storage disease. Obstet Gynecol ;— Dagli AI, Lee PJ, Correia CE, et al. Pregnancy in glycogen storage disease type Ib: gestational care and report of first successful deliveries.

Chou JY, Mansfield BC. Mutations in the glucosephosphatase-alpha G6PC gene that cause type Ia glycogen storage disease. Hum Mutat. Franco LM, Krishnamurthy V, Bali D, et al. Hepatocellular carcinoma in glycogen storage disease type Ia: a case series.

Lewis R, Scrutton M, Lee P, Standen GR, Murphy DJ. Antenatal and Intrapartum care of a pregnant woman with glycogen storage disease type 1a. Eur J Obstet Gynecol Reprod Biol. Ekstein J, Rubin BY, Anderson, et al.

Mutation frequencies for glycogen storage disease in the Ashkenazi Jewish Population. Am J Med Genet A. Melis D, Parenti G, Della Casa R, et al. Brain Damage in glycogen storage disease type I.

J Pediatr. Rake JP, Visser G, Labrune, et al. Guidelines for management of glycogen storage disease type I-European study on glycogen storage disease type I ESGSD I.

Eur J Pediatr. Rake JP Visser G, Labrune P, et al. Glycogen storage disease type I: diagnosis, management, clinical course and outcome.

Results of the European study on glycogen storage disease type I EGGSD I. Eur J Pediat. Chou JY, Matern D, Mansfield, et al. Lee PJ, Dixon MA, Leonard JV Uncooked cornstarch-efficacy in type I glycogenosis.

Arch Dis Child — Article CAS PubMed Central PubMed Google Scholar. Mairovitz V, Labrune P, Fernandez H, Audibert F, Frydman R Pregnancy and contraception in women with glycogen storage disease type I. Matern D, Starzl TE, Arnaout W, Barnard J, Bynon JS, Dhawan A, Emond J, Haagsma EB, Hug G, Lachaux A, Smit GP, Chen YT Liver transplantation for glycogen storage disease types I, III, and IV.

Eur J Pediatr [Suppl 2]: SS Article PubMed Central PubMed Google Scholar. Narisawa K, Otomo H, Igarashi Y, Arai N, Otake M, Tada K, Kuzuya T Glycogen storage disease type 1b: microsomal glucosephosphatase system in two patients with different clinical findings.

Rake JP, Huismans D, Visser G, Piers DA, Smit GPA Osteopenia in glycogen storage disease type I. BIMDG News-letter Spring: 27— Rake JP, Berge AM ten, Visser G, Verlind E, Niezen-Koning KE, Buys CHCM, Smit GPA, Scheffer H Glycogen storage disease type Ia: recent experience with mutation analysis, a summary of mutations reported in the literature and a newly developed diagnostic flowchart.

Rake JP, Visser G, Labrune Ph, Leonard JV, Ullrich K, Smit GPA Glycogen storage disease type I: diagnosis, management, clinical course and outcome. Results of the European Study on Glycogen Storage Disease Type I ESGSD I. Eur J Pediatr DOI Reitsma-Bierens WC Renal complications in glycogen storage disease type I.

Reitsma-Bierens WC, Smit GP, Troelstra JA Renal function and kidney size in glycogen storage disease type I. Pediatr Nephrol 6: — Restaino I, Kaplan BS, Stanley C, Baker L Nephrolithiasis, hypocitraturia, and a distal renal tubular acidification defect in type 1 glycogen storage disease.

Smit GPA, Berger R, Potasnick R, Moses SW, Fernandes J The dietary treatment of children with type I glycogen storage disease with slow release carbohydrate.

Smit GPA, Ververs MT, Belderok B, van Rijn M, Berger R, Fernandes J Complex carbohydrates in the dietary management of patients with glycogenosis caused by glucosephosphatase deficiency. Am J Clin Nutr 95— CAS PubMed Google Scholar. Thorton PS Renal disease in glycogen storage disease type I.

BIMDG Spring: 24— Ubels FL, Rake JP, Slaets JPJ, Smit GPA, Smit AJ Is glycogen storage disease Ia associated with atherosclerosis.

Veiga-da-Cunha M, Gerin I, Chen YT, Lee PJ, Leonard JV, Maire I, Wendel U, Vikkula M, Van Schaftingen E The putative glucosephosphate translocase is mutated in essentially all cases of glycogen storage disease types I non-a.

Eur J Hum Genet 7: — Visser G, Rake JP, Fernandes J, Labrune Ph, Leonard JV, Moses SW, Ullrich K, Smit GPA Neutropenia, neutrophil dysfunction and inflammatory bowel disease in glycogen storage disease type Ib.

Results of the European Study on Glycogen Storage Disease Type I. Visser G, Rake JP, Labrune P, Leonard JV, Moses S, Ullrich K, Wendel U, Groenier KH, Smit GPA Granulocyte colony-stimulating factor in glycogen storage disease type 1b.

Results of the European Study on Glycogen Storage Disease Type 1. Visser G, Rake JP, Labrune P, Leonard JV, Moses S, Ullrich K, Wendel U, Smit GPA Consensus guidelines for management of glycogen storage disease type 1b—European Study on Glycogen Storage Disease Type 1.

Weinstein DA, Somers MJ, Wolfsdorf JI Decreased urinary citrate excretion in type 1a glycogen storage disease. Wolfsdorf JI, Crigler JF Cornstarch regimens for nocturnal treatment of young adults with type I glycogen storage disease. Am J Clin Nutr — Wolfsdorf JI, Crigler JF Effect of continuous glucose therapy begun in infancy on the long-term clinical course of patients with type I glycogen storage disease.

J Pediatr Gastroenterol Nutr — Wolfsdorf JI, Keller RJ, Landy H, Crigler JF Glucose therapy for glycogenosis type 1 in infants: comparison of intermittent uncooked cornstarch and continuous overnight glucose feedings. Wolfsdorf JI, Laffel LM, Crigler JF Metabolic control and renal dysfunction in type I glycogen storage disease.

Download references. Peter A. Service Pédiatrie 1, Hôpital Antoine-Béclère, Clamart, France. Institute of Child Health, Great Ormond Street Hospital, London, UK. Department of Paediatrics, University Hospital Hamburg, Germany.

You can also search for this author in PubMed Google Scholar. Correspondence to Jan Peter Rake. On behalf of the participating members of the ESGSD I.

Members of the ESGSD I are: Austria W Endres, D Skladal, Innsbruck , Belgium E Sokal, Brussels , Czech Republic J Zeman, Prague , France P Labrune, Clamart , Germany P Bührdel, Leipzig, K Ullrich, Hamburg, G Däublin, U Wendel, Düsseldorf , Great Britain P Lee, JV Leonard, G Mieli-Vergani, London , Hungary L Szönyi, Budapest , Italy P Gandullia, R Gatti, M di Rocco, Genoa, D Melis, G Andria, Naples , Israel S Moses, Beersheva , Poland J Taybert, E Pronicka, Warsaw , The Netherlands JP Rake, GPA Smit, G Visser, Groningen , Turkey H Özen, N Kocak, Ankara.

Reprints and permissions. Rake, J. et al. Guidelines for management of glycogen storage disease type I—European study on glycogen storage disease type I ESGSD I. Eur J Pediatr , S—S Download citation. Published : 02 May Issue Date : October Anyone you share the following link with will be able to read this content:.

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Last updated: December 23, Years published: Forskolin and hair growth,, Natural anthocyanins sources,Maagement, NORD gratefully acknowledges Management of glycogen storage disease Bali, PhD, Sisease, Division of Medical ov, Department atorage Pediatrics, Duke Herbal allergy remedies Co-Director, Biochemical Genetics Laboratories, Duke University Health System, and Yuan-Tsong Glycpgen, MD, PhD, Professor, Division of Medical Genetics, Department of Pediatrics, Duke Medicine; Distinguished Research Fellow, Academia Sinica Institute of Biomedical Sciences, Taiwan for assistance in the preparation of this report. Glycogen storage diseases are a group of disorders in which stored glycogen cannot be metabolized into glucose to supply energy and to maintain steady blood glucose levels for the body. Type I glycogen storage disease is inherited as an autosomal recessive genetic disorder. Glycogen storage disease type I GSDI is characterized by accumulation of excessive glycogen and fat in the liver and kidneys that can result in an enlarged liver and kidneys and growth retardation leading to short stature.

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Diagnosing Glycogen Storage Disease. There are several types of glycogen storage disease. The most common are: GSD type 0 Lewis disease GSD type I Von Gierke disease GSD type II Pompe disease GSD type III Cori or Forbes disease GSD type IV Andersen disease, Adult Polyglucosan Body Disease GSD type V McArdle disease GSD type VI Hers disease GSD type VII Tarui disease GSD type IX GSD type XI Fanconi-Bickel syndrome GSD type XV Polyglucosan body myopathy 2.

Our Locations. Duke Health offers locations throughout the Triangle. Find one near you. Find a Location. Managing the Complications of Glycogen Storage Diseases.

Complications vary depending on the type of glycogen storage disease; however, they can include: Liver problems Low blood sugar Gastrointestinal concerns such as inflammatory bowel disease Growth and developmental delays Lung problems Heart problems Additional complications can include muscle disease, blood disorders, and kidney problems.

Call for an Appointment. Preventive Disease Monitoring Living with glycogen storage disease means closely monitoring lab test results, as well as regular tests and screening to diagnose complications when they arise.

Best Children's Hospital in NC. Blood Tests May be used to monitor the health of the liver, kidneys, and muscles, and ensure proper blood sugar levels.

GSDI is associated with abnormalities mutations in the G6PC gene GSDIA or SLC37A4 gene GSDIB. These mutations result in enzyme deficiencies that block glycogen breakdown in affected organs causing excess amounts of glycogen and fat accumulation in the body tissues and low levels of circulating glucose in the blood.

The enzyme deficiency also results in an imbalance or excessive accumulation of other metabolites, especially lactates, uric acid and fats like lipids and triglycerides. The primary symptom of GSDI in infancy is a low blood sugar level hypoglycemia. Symptoms of GSDI usually begin at three to four months of age and include enlargement of the liver hepatomegaly , kidney nephromegaly , elevated levels of lactate, uric acid and lipids both total lipids and triglycerides , and possible seizures caused due to repeated episodes of hypoglycemia.

Continued low blood sugar can lead to delayed growth and development and muscle weakness. Affected children typically have doll-like faces with fat cheeks, relatively thin extremities, short stature, and protuberant abdomen.

High lipid levels can lead to the formation of fatty skin growths called xanthomas. Other conditions that can be associated with untreated GSD1 include; osteoporosis, delayed puberty, gout arthritis caused by accumulation of uric acid , kidney disease, pulmonary hypertension high blood pressure in the arteries that supply the lungs , hepatic adenoma benign liver tumors , polycystic ovaries in females, an inflammation of the pancreas pancreatitis , diarrhea and changes in brain function due to repeated episodes of hypoglycemia.

Impaired platelet function can lead to a bleeding tendency with frequent nose bleeds epistaxis. In general GSD type Ib patients have similar clinical manifestations as type Ia patients, but in addition to the above mentioned manifestations, GSDIb is also associated with impaired neutrophil and monocyte function as well as chronic neutropenia after the first few years of life, all of which result in recurrent bacterial infections and oral and intestinal mucosal ulcers.

Early diagnosis and effective treatment can result in normal growth and puberty and many affected individuals live into adulthood and enjoy normal life activities. Many female patients have had successful pregnancies and childbirth.

Type I glycogen storage disease is associated with abnormalities in two genes. This type of GSDI is termed glycogen storage disease type Ia.

This type of GSDI is termed glycogen storage disease type Ib. Both these enzyme deficiencies cause excess amounts of glycogen along with fats to be stored in the body tissues. Recessive genetic disorders occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms.

The risk is the same for males and females. Type I glycogen storage disease occurs in approximately 1 in , births. The prevalence of GSDI in Ashkenazi Jews is approximately 1 in 20, This condition affects males and females in equal numbers in any given population group.

Symptoms of the following disorders can be similar to those of glycogen storage disease type I. Detailed evaluations may be useful for a differential diagnosis:.

Forbes or Cori disease GSD-III is one of several glycogen storage disorders that are inherited as autosomal recessive traits. Symptoms are caused by a lack of the enzyme amylo-1,6 glucosidase debrancher enzyme.

This enzyme deficiency causes excessive amounts of an abnormally digested glycogen the stored form of energy that comes from carbohydrates to be deposited in the liver, muscles and, in some cases, the heart.

In the first few months some symptoms may overlap with GSDI elevated lipids, hepatomegaly, low glucose. Andersen disease GSD-IV also known as glycogen storage disease type IV; This GSD is also inherited as an autosomal recessive trait.

In most affected individuals, symptoms and findings become evident in the first few years of life. Such features typically include failure to grow and gaining weight at the expected rate failure to thrive and abnormal enlargement of the liver and spleen hepatosplenomegaly.

Hers disease GSD-VI is also called glycogen storage disease type VI. It usually has milder symptoms than most other types of glycogen storage diseases.

It is caused by a deficiency of the enzyme liver phosphorylase. Hers disease is characterized by enlargement of the liver hepatomegaly , moderately low blood sugar hypoglycemia , elevated levels of acetone and other ketone bodies in the blood ketosis , and moderate growth retardation.

Symptoms are not always evident during childhood, and children are usually able to lead normal lives. However, in some instances, symptoms may be severe.

Glycogen storage disease IX is caused due to deficiency of phosphorylase kinase enzyme PK enzyme deficiency.

The disorder is characterized by slightly low blood sugar hypoglycemia. Excess amounts of glycogen the stored form of energy that comes from carbohydrates are deposited in the liver, causing enlargement of the liver hepatomegaly.

Hereditary Fructose intolerance HFI is an autosomal recessive genetic condition that causes an inability to digest fructose fruit sugar or its precursors sugar, sorbitol and brown sugar.

This is due to a deficiency of activity of the enzyme fructosephosphate aldolase Aldolase B , resulting in an accumulation of fructosephosphate in the liver, kidney, and small intestine.

Fructose and sucrose are naturally occurring sugars that are used as sweeteners in many foods, including many baby foods. This disorder can be life threatening in infants and ranges from mild to severe in older children and adults.

GSD type I is diagnosed by laboratory tests that indicate abnormal levels of glucose, lactate, uric acid, triglycerides and cholesterol. Molecular genetic testing for the G6PC and SLC37A4 genes is available to confirm a diagnosis. Molecular genetic testing can also be used for carrier testing and prenatal diagnosis.

Liver biopsy can also be used to prove specific enzyme deficiency for GSD Ia. Treatment GSDI is treated with a special diet in order to maintain normal glucose levels, prevent hypoglycemia and maximize growth and development. Frequent small servings of carbohydrates must be maintained during the day and night throughout the life.

Calcium, vitamin D and iron supplements maybe recommended to avoid deficits. Frequent feedings of uncooked cornstarch are used to maintain and improve blood levels of glucose.

Allopurinol, a drug capable of reducing the level of uric acid in the blood, may be useful to control the symptoms of gout-like arthritis during the adolescent years. Human granulocyte colony stimulating factor GCSF may be used to treat recurrent infections in GSD type Ib patients.

Liver tumors adenomas can be treated with minor surgery or a procedure in which adenomas are ablated using heat and current radiofrequency ablation.

Individuals with GSDI should be monitored at least annually with kidney and liver ultrasound and routine blood work specifically used for monitoring GSD patients. Information on current clinical trials is posted on the Internet at www.

All studies receiving U. government funding, and some supported by private industry, are posted on this government web site. For information about clinical trials being conducted at the National Institutes of Health NIH in Bethesda, MD, contact the NIH Patient Recruitment Office:.

Tollfree: TTY: Email: prpl cc. For information about clinical trials sponsored by private sources, contact: www. TEXTBOOKS Chen YT, Bali DS.

Prenatal Diagnosis of Disorders of Carbohydrate Metabolism. In: Milunsky A, Milunsky J, eds. Genetic disorders and the fetus — diagnosis, prevention, and treatment. West Sussex, UK: Wiley-Blackwell; Chen Y. Glycogen storage disease and other inherited disorders of carbohydrate metabolism.

In: Kasper DL, Braunwald E, Fauci A, et al. New York, NY: McGraw-Hill; Weinstein DA, Koeberl DD, Wolfsdorf JI. Type I Glycogen Storage Disease. In: NORD Guide to Rare Disorders. Philadelphia, PA: Lippincott, Williams and Wilkins; JOURNAL ARTICLES Chou JY, Jun HS, Mansfield BC.

J Inherit Metab Dis. doi: Epub Oct 7. PubMed PMID: Kishnani PS, Austin SL, Abdenur JE, Arn P, Bali DS, Boney A, Chung WK, Dagli AI, Dale D, Koeberl D, Somers MJ, Wechsler SB, Weinstein DA, Wolfsdorf JI, Watson MS; American College of Medical Genetics and Genomics. Genet Med. Austin SL, El-Gharbawy AH, Kasturi VG, James A, Kishnani PS.

Menorrhagia in patients with type I glycogen storage disease. Obstet Gynecol ;— Dagli AI, Lee PJ, Correia CE, et al. Pregnancy in glycogen storage disease type Ib: gestational care and report of first successful deliveries. Chou JY, Mansfield BC. Mutations in the glucosephosphatase-alpha G6PC gene that cause type Ia glycogen storage disease.

Hum Mutat. Franco LM, Krishnamurthy V, Bali D, et al.

It is an inherited glycpgen that affects the metabolism — Natural anthocyanins sources way the body breaks food Managememt into energy. After we Improve cognitive strength, excess Herbal alternative medicine is dissease Management of glycogen storage disease the fo as glycogen to maintain normal glucose levels in our body. In GSD I, the enzyme needed to release glucose from glycogen is missing. When this occurs, a person cannot maintain his or her blood glucose levels and will develop hypoglycemia low blood sugar within a few hours after eating. The low levels of glucose in the blood of these individuals often result in chronic hunger, fatigue, and irritability. Searching glycogenn just a few words should be Natural anthocyanins sources to get started. If ot need visease make more Management of glycogen storage disease queries, use the tips below to guide EGCG and inflammation-related diseases. The glycogen storage diseases Glycoten Management of glycogen storage disease a group of inherited metabolic disorders that result from Injury recovery eating defect in any one of several enzymes required for either glycogen synthesis or glycogen degradation. The GSDs can be divided into those with hepatic involvement, which present as hypoglycemia, and those which are associated with neuromuscular disease and weakness. The severity of the GSDs range from those that are fatal in infancy if untreated to mild disorders with a normal lifespan. The diagnosis, treatment, and prognosis for the common types of GSDs are reviewed. Broadly speaking, the GSDs can be divided into those with hepatic involvement, which present as hypoglycemia, and those which are associated with neuromuscular disease and weakness Table 1 [ 1 ].