Glycogen Storage Diseases Types I-VII Clinical Presentation

Updated: Jul 28, 2017
  • Author: Catherine Anastasopoulou, MD, PhD, FACE; Chief Editor: George T Griffing, MD  more...
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GSD type I

The earliest signs of disease may develop shortly after birth and are usually symptoms of hypoglycemia. Patient's may present with irritability, pallor, cyanosis, hypotonia, tremors, loss of consciousness, apnea and seizures. The median age of symptom presentation is usually four to six months. 

Some children have diarrhea due to pseudocolitis.

GSD type II

Symptoms of the infantile form usually begin in infants at the end of the second month of life, with profound hypotonia and heart failure. Muscle weakness progresses rather rapidly, manifesting as respiratory and feeding difficulties.  An early onset “nonclassic” phenotype has also been described in these cases, hypotonia without cardiomyopathy develops during the first and second year of life.

In the juvenile form, the initial clinical symptoms appear in persons aged 1-15 years. Retarded motor development, hypotonia, and muscle weakness due to slowly progressive skeletal muscle disease characterize the juvenile form. Intellectual development is normal. Atony of the anal sphincter and enlargement of the urinary bladder can be found in only a minority of children.

The adult form develops in persons aged 10-30 years and, less commonly, later. Its course progresses slowly. Dyspnea due to the involvement of respiratory muscles and difficulties in climbing up the stairs caused by proximal myopathy are the leading clinical manifestations. In one third of patients, the initial symptoms are somnolence, morning headaches, orthopnea, and exertional dyspnea. Weakness of the respiratory muscles, particularly the diaphragm, causes these symptoms. [22]

GSD type III

The first manifestations of the disease usually appear in infants one year of age, although in milder variants, the onset may be delayed into childhood. The symptoms are much less severe than in GSD type 1, and only about half of the patients present with severe hypoglycemia. Hepatomegaly is the most common presenting symptom on routine examination which then prompts further investigation. Other signs such as growth retardation, hyperlipidemia and fasting ketotic hypoglycemia can also be seen. [7, 17]

Liver disease is less common in adolescents and adults. In childhood, weakness and muscle fatigue secondary to skeletal myopathy is less prominently seen. This is in contrast to adulthood where muscle weakness is more commonly seen because of progression of muscle damage and disease . Cardiovascular abnormalities can further dominate the clinical presentation of the disease depending on severity of cardiac involvement. Patients with GSD IIIa may present with hypertrophic cardiomyopathy in which the disease course can range from asymptomatic to severe. [6]

GSD type IV

Children affected with GSD type IV are born without signs of the disease, although some of them may have a dysmorphic face. However, in the weeks after birth, failure to thrive, hypotonia, and atrophy of the muscles are noted. (see physical)

GSD type V

The classic form appears in persons aged 10-20 years, most in first decade of life. Degree of exercise intolerance varies per individual. Symptoms are usually exacerbated with sustained aerobic or isometric exercise. [19]  Patients commonly report fatigue during physical exertion, muscle cramps, and later, muscle weakness and burgundy red–colored urine. Patients with GSD type V may also present with the "second wind phenomenon" in which patients have quick relief of muscular fatigue with rest and are then able to resume physical activity without significant symptoms. [19]

GSD type VI

Symptoms, if present, are minimal. Often, patients seek help for retarded growth and prominent hepatomegaly. Hypoglycemia ranges from mild to severe, with ketotic hypoglycemia after fasting. Hypoglycemia can present during pregnancy. 

GSD type VII

Similar to that of GSD type V, intolerance of physical activity, muscle cramps, and burgundy red–colored urine occur during a rhabdomyolysis episode. [21]   

Attacks of rhabdomyolysis may be associated with nausea and vomiting, and more often than not, a meal rich in carbohydrates is consumed beforehand.



GSD type I

A leading sign of GSD type I is enlargement of the liver and kidneys. Enlargement of the abdomen due to hepatomegaly can be the first sign noted by the patient's mother. During the first weeks of life, the liver is normal size.It enlarges gradually thereafter, and in some patients, it even reaches the symphysis.  

Because of fat deposition in the cheeks, patient's characteristically resemble a doll's face. See the image below. 

An infant with glycogen storage disease type Ia. N An infant with glycogen storage disease type Ia. Note the typical facial aspect resembling a doll's face.

Mental development proceeds normally.

Growth failures, as described as short stature and thin legs, are commonly seen in children affected by GSD type 1. Affected children never gain the height otherwise expected from the genetically determined potential of their families. The patient's height is usually below the third percentile for their age. The onset of puberty is delayed. See the image below.

A child with glycogen storage disease type Ia. A child with glycogen storage disease type Ia.

Skin and mucous membrane changes include the following:

  • Eruptive xanthomas develop on the extensor surfaces of the extremities.

  • Tophi or gouty arthritis may occur. Uric tophi often have the same distribution as xanthomas.

  • Spider angiomas may be present.

  • Perianal and gingival abscesses of the oral mucosa and gums may be observed. Aphthous ulcers are often present in patients with GSD type Ib.

  • Perianal erythema and erosions may occur in patients with prolonged diarrhea due to pseudocolitis.

  • In a 2002 report, Visser et al [23] presumed that the main cause of disturbed intestinal function is loss of the integrity of the mucosal barrier, which occurs as a result of inflammation, and loss of neutrophil function, which often occurs in patients with GSD lb.

Risk factors and adverse events are as follows:

  • Foods rich in fructose, galactose, and triglycerides adversely affect the long-term complications caused by lactic acidosis, hyperuricemia, and hyperlipidemia.

  • Hypoglycemia and infections are frequent.

GSD type II

Heavy deposits of glycogen in the heart, liver, and tongue characterize the infantile form; as a result of the deposits, these tissues enlarge.

Conspicuous cardiomegaly with cardiomyopathy and heart failure may be present. Macroglossia, tongue fasciculation and moderate hepatomegaly may be noted.

Generalized severe hypotonia and muscle weakness that involves skeletal and respiratory muscles, as well as. delayed motor milestones, feeding and swallowing difficulties are characteristics.  The affected skeletal muscles are firm on palpation and, occasionally, hypertrophic. In some patients. Signs of respiratory insufficiency are due to the involvement of respiratory musculature. Spontaneous movements are scarce, and painful stimuli cause weak motor reactions. Tendon reflexes are diminished or absent. Mental functions are retained.

In the CNS, the disease primarily affects the nuclei of the brainstem and the cells of the ventral horn of the spinal cord. Mental functions are preserved.

Juvenile form

Respiratory insufficiency and hypotonia largely of the proximal musculature are present. Macroglossia, cardiomegaly, cardiomyopathy, and hepatomegaly usually are absent.

Adult form

Proximal muscle weakness (difficulty rising from a chair or climbing stairs). Muscle volume is decreased, and tendon reflexes are diminished.  Waddling gait, Gower sign, Trendelenburg sign are seen, the visceral organs are not affected; however, intracranial aneurysms are possible because of glycogen deposits in the smooth muscle cells of the cerebral arteries. Cardiomyopathy is not a feature of the adult form. 

GSD type III

GSD type III is a heterogeneous disease. Two subtypes exist: GSD type IIIa and GSD type IIIb. In most patients, the liver is enlarged. In some children, growth retardation, renal tubular dysfunction, liver adenomas, liver cirrhosis can be observed.

GSD type IIIa is more common (approximately 85%) and prognostically more unfavorable than other forms. Hepatomegaly and/or splenomegaly are present with elevated liver transaminases. Muscular weakness and atrophy, particularly of the girdle and limb musculature, may be observed. Cardiomegaly and cardiomyopathy may occur which can lead to heart failure and possibly sudden death.Cardiac and skeletal muscle abnormalities taking on a progressive course and possibly appearing at different ages (from early childhood to late adulthood) may be noted.

GSD type IIIb is less common (approximately 15%) although prognostically more favorable than other forms. The liver is the only organ involved. Hepatosplenomegaly is moderate. Mild fibrosis and micronodular cirrhosis of the liver are rare and often clinically silent. Hepatomegaly is pronounced during childhood but usually normalizes at puberty. Growth is accelerated at puberty; therefore, most patients reach their expected height.

GSD type IV

Presentation varies depending on the mutation, however, 5 frequent subtypes have been identified: [18]

Hepatic predominant forms:

  • Classic (progressive) hepatic subtype. Failure to thrive, hepatomegaly, liver dysfunction, progressive liver scarring with portal hypertension, ascites, and esophageal varices, jaundice, hypotonia, and cardiomyopathy. Hypoglycemia may develop later in the course of the disease. Disease is evident during the first 18 months of life. Death typically by age five years from liver failure
  • Non-progressive hepatic subtype. Liver dysfunction, myopathy, and hypotonia in childhood.

Neuromuscular predominant forms:

  • Fatal perinatal neuromuscular subtype. Presents in utero with fetal akinesia deformation sequence (FADS):  Decreased fetal movements, multiple contractures, polyhydramnios, hydrops fetalis, hypotonia, cardiac dysfunction and perinatal death. 
  • Congenital neuromuscular subtype. Presents with severe hypotonia at birth, respiratory distress, dilated cardiomyopathy, weakness, muscle atrophy and early infantile death. 
  • Childhood neuromuscular subtype. Presents with skeletal myopathy (weakness, fatigue, exercise intolerance, atrophy), and occasionally with dilated cardiomyopathy, arrhythmias and heart failure.
  • Adult Polyglucosan body disease. Rare variant, presents with upper and lower motor neuron symptoms, urinary incontinence, sensory deficits, gait disturbances, autonomic dysfunction and cognitive impairment.

GSD type V

In a milder variety, the first symptoms and signs may appear late, even in elderly patients. 

Forms clinically expressed in the first years of life occur with muscle hypotonia and generalized muscle weakness and occasionally lead to respiratory insufficiency.

Myoglobinuria from repeated strenuous exercise can be a cause of renal failure.

GSD type VI

GSD type VI is a benign disease.

At times, hepatomegaly is incidentally noted during an investigation of the child's slow growth.

Skeletal and cardiac muscles are unaffected.

With age, the size of the liver decreases and normalizes at or around puberty.

No intellectual abnormalities.

GSD type VII

GSD type VII is more severe than GSD type V.

Rhabdomyolysis with renal failure is common.

In some patients, erythrocyte hemolysis occurs.

Jaundice is apparent in severe hemolysis.

Two rare varieties of GSD type VII exist. One form occurs in infants with hypotonia and weakness of the extremity muscles; this form progresses in severity, with a lethal outcome in early childhood. The other form occurs in young adults or older persons; this form progresses slowly, and its clinical presentation is dominated by the weakness of the different muscle groups rather than the muscle cramps and myoglobinuria.



GSD type I

GSD type Ia

G6Pase deficiency is the cause of GSD type Ia. G6Pase is an enzyme that hydrolyzes glucose-6-phosphatase into free glucose and a phosphate group.Mutations in the transmembrane helices of the protein cause the most severe deficiency of enzyme activity.

Two different G6Pase enzymes are known. Glucose-6-phosphatase-alpha (G6Pase-alpha), located in the liver, kidney, and intestine, is solely responsible for the final stages of gluconeogenesis and glycogenolysis and for releasing glucose to the blood. Glucose-6-phosphatase-beta (Glc-6-Pase-beta) is also able to hydrolyze G6P to glucose and is an integral membrane protein in the endoplasmic reticulum. It contains 9 transmembrane domains, like G6Pase-alpha, but is ubiquitously expressed, similar to G6PT, and does not participate in blood glucose homeostasis between meals.

It seems that endoplasmic reticulum G6Pase-beta and G6PT complex is necessary for endogenous production of glucose during specific stress situations in some tissue cells, such as astrocytes, peripheral neutrophils, and bone marrow myelocytes.

The G6Pase gene is located on band 17q21 as a single copy. The complementary DNA (cDNA) has been cloned, and the most frequent mutations are known,most of which of missense/nonsense mutations. For optimal catalytic activity, critical residues are 347-354. The gene contains 5 exons and spans approximately 12.5 kb. An analysis of the G6Pase gene in 70 unrelated patients with enzymatically confirmed diagnosis of GSD type Ia revealed that the most frequent mutations were R83C and Q347X in Caucasians, 130X and R83C in Hispanics, and R83H in Chinese.

The Q347X mutation was found only in whites, and 130X was found only in Hispanic patients. A mutational analysis in French patients has been published; this analysis reveals 14 different mutations. The most common among them, in as many as 75% of mutated alleles, were Q347X, R83C, D38V, G188R, and 158Cdel.

At present, at least 56 mutations in the G6Pase gene have been reported in patients with GSD type Ia. The mutated allele is inherited as an autosomal recessive trait. No strong evidence indicates a clear genotype-phenotype correlation, but in 2002, Matern et al [24] reported a relationship between (1) a G188R mutation and GSD type I non–a phenotype and a homozygous G727T mutation and (2) a milder form of clinical presentation but with a higher risk for hepatocellular malignancy. On the other hand, in 2005 Melis et al [25] did not find a correlation between individual mutations and the presence of neutropenia, bacterial infections, and systemic complications in patients with GSD type Ib.

Early prenatal genetic diagnosis of disease is possible using chorionic villi or amniocytic DNA samples instead of invasive fetal liver biopsy.

GSD type Ib

Deficiency of G6PT1 translocase causes GSD type Ib. The G6PT1 gene is expressed in liver, kidney, and hematopoietic progenitor cells, spans approximately 5 kb and contains 8 exons, and has been mapped to band 11q23. The mutated allele is inherited as an autosomal recessive trait. There is no correlation between the kind of mutation in the G6PT gene and severity of the disease. Therefore, other unknown factors are believed to be responsible for expression of different symptoms, such as neutropenia, in these patients, which dramatically influences the severity and natural course of the disease.

In 2003, Kuijpers et al found circulating neutrophils with signs of apoptosis and increased caspase activity in 5 patients with GSD type Ib. However, granulocyte colony–stimulating factor in in vitro cultures did not influence apoptosis. [26]

In 2007, Cheung et al suggested that the G6Pase-beta/G6PT complex might be functional in neutrophils and in myeloid cells. Therefore, defects in GSD-Ib might be a result of loss in activity of that complex, leading to an increasing rate of neutrophil apoptosis and impairment of hematopoiesis in the bone marrow, with neutropenia and increasing susceptibility to bacterial infections as a consequence. [27]

The G6PT1 gene is strongly expressed in liver, kidney, and hematopoietic progenitor cells, which might explain major clinical symptoms such as hepatomegaly, nephromegaly, and neutropenia in GSD type Ib.

In a 2005 multicentric study and review of the literature, Melis et al from Italy concluded that there is no correlation between individual mutations and the presence of neutropenia, bacterial infections, and systemic complications and suggested that different genes and proteins could be involved in differentiation, maturation, and apoptosis of neutrophils and the severity and frequency of infections. They also found no detectable mutations in 3 patients, indicating that the second protein may play a role in microsomal phosphate transport. [25]

GSD type Ic

Deficiency of T2 translocase causes GSD type Ic. The GSD type Ic gene is mapped to bands 11q23. The mutated allele is inherited as an autosomal recessive trait. In 1999, Janecke et al confirmed that GSD type Ic is allelic to GSD type Ib. [28]

GSD type Id

Deficiency of T3 transposes causes GSD type Id. The gene is mapped to bands 11q23-q24. The mutated allele is inherited as an autosomal recessive trait.

GSD type II

Deficiency of the acid alpha-1,4-glucosidase  (GAA) coded on bands 17q21.2-q23 causes GSD type II. The GAA gene is 20 kb in length, contains 20 exons, and codes for a 105-kd protein. The mutated allele is inherited as an autosomal recessive trait. The disease is expressed in homozygotic carriers of the mutation. Heterozygotic carriers of the mutation do not show signs of the disease. Thus far, a large number of different mutations (eg, missense, nonsense, deletion, splice site mutations) have been found, and various forms of enzyme deficiency may result from the following mutations: complete loss of the protein (infantile form), decreased enzymatic activity due to reduced affinity for substrate (juvenile and adult forms), and decreased levels of the protein with normal substrate affinity (juvenile and adult forms, IVS1-13T-->G splice site mutation common in adults). Some patients, mostly in Asian populations, are homozygous for a pseudodeficiency allele [c.1726 G>A (p. Gly576Ser)]. [29]

GSD type III

A deficiency of the debrancher enzyme causes the disease. In GSD type IIIb, the enzyme deficit is confined to the liver, whereas in GSD type IIIa, the deficit also occurs in the skeletal muscles and the myocardium. A correlation exists between the residual enzyme activity and the severity of the clinical presentation. A gene mapped to band 1p21 codes the enzyme. More than 30 different mutations have been identified in patients from many different ethnic groups. The cDNA has been cloned. The gene contains 7072 base pairs (bp), of which 4596 bp is in the coding region. Hepatic and muscular messenger RNA (mRNA) differs in the 5' region. Genetic heterogeneity is found at the mRNA level. The disease is inherited as an autosomal recessive trait. Carrier detection and prenatal diagnosis are possible by DNA mutation analysis.

GSD type IV

Amylo-1,4-1,6-transglucosidase or brancher enzyme deficiency is the cause of this disease. A gene mapped to band 3p12 codes the brancher enzyme. The full-length cDNA is approximately 3 kb. The coding sequence contains 2106 bp that encodes a protein of 702 amino acids. There is a correlation between the various gene mutations and the severity of the clinical manifestations (eg, 210-bp DNA deletion in a patient with fatal neonatal neuromuscular form, Y329S point mutation in a patient with nonprogressive hepatic form). The disease is inherited as an autosomal recessive trait. Carrier detection and prenatal diagnosis are available by DNA analysis. Further research is needed to determine whether certain mutations may be associated with particular variants of the disease.

GSD type V

Myophosphorylase (glycogen phosphorylase) deficiency causes the disease. Myophosphorylase exists in different tissue-specific isoforms (eg, muscle, liver, brain), and a separate gene codes enzyme isoforms in each tissue. The PYGM gene, located on 11q13 codes for myophosphorylase and most mutations are found between exon 1 to 17. More than 50% of the gene mutations found have been missense. [30]  The most common is C-to-T transition at codon 49 in exon 1. The most prevalent mutations in white and Japanese patients are R49X and deletion F708, respectively. Rare mutations include G-to-A transition at codon 204 in exon 5 and A-to-G transversion at codon 542 in exon 14. All other rare mutations occur in approximately fewer than 30% of patients. In 2002, Dimaur et al reported that the mutations in patients with GSD type V are spread throughout the gene and that no clear genotype-phenotype correlation exists. GSD type V is inherited as an autosomal recessive trait. [31]

GSD type VI

Hepatic phosphorylase deficiency or deficiency of other enzymes (eg, adenylate cyclase, protein kinase A, phosphorylase kinase) that form a chain of reactions necessary for the activation of phosphorylase causes GSD type VI. Heterogeneity exists in the clinical symptoms as a result of the different PYGL gene defects observed in affected individuals; they vary from hepatomegaly and subclinical hypoglycemia to severe hepatomegaly, hypoglycemia, and lactic acidosis.

The hepatic phosphorylase gene is located on bands 14q21-q22. Mutations responsible for the disease have been identified. Phosphorylase b kinase exists in an inactive form that is activated by the cyclic adenosine monophosphate (cAMP)–dependent protein kinase. The several subunits of phosphorylase kinase are coded by separate genes located on somatic chromosomes (subunits a and c) and the X chromosome (subunit b). A terminological confusion exists when classifying hepatic phosphorylase b kinase deficiencies. Some authors place all the forms under the name GSD type VI, whereas other authors label phosphorylase b kinase deficiency as GSD type IX and cAMP-dependent protein kinase deficiency as GSD type X.

The X-linked form of hepatic phosphorylase kinase deficiency is the most common (75%) among patients with GSD type VI. The gene is located on the short arm of the X chromosome at band p22.

Other forms of GSD type VI are inherited as an autosomal recessive trait.

GSD type VII

PFK deficiency causes GSD type VII. The PFKM locus was assigned to band 1cen-q32 by somatic cell hybridization. The genomic organization of cDNA is known. In 1996, Howard et al, [32] based on physical and genetic mapping, concluded that the PFKM gene is located on band 12q13.3 instead of chromosome 1, as previously believed. The different allelic variants of mutations are detected up to now. The inheritance is autosomal recessive.



GSD type I

Long term complications for GSD type 1a and 1b include [33]

  • Renal: Later complications of disease include renal function disturbances including nephrocalcinosis, hematuria, proteinuria and hypertension. Nephromegaly is seen secondary to glycogen deposition in the kidney. Renal insufficiency may progress to end stage renal disease, requiring dialysis and transplantation. [34]
  • Neurocognitive Deficits: Patients with GSD have normal IQ, but because of frequent hypoglycemic episodes, brain function is altered. 
  • Anemia
  • Bleeding Diathesis: Some patients may bleed easily, usually in the form of epistaxis, easy bruising, or heavy menses. Caution is to be taken during surgical procedures. This tendency is a result of altered platelet function, due to reduced or dysfunctional von Willebrand factor. 
  • Osteoporosis: Bone mineral density can be severely reduced in more than half the patients with GSD type 1 mainly because of lack of vitamin D in the diet. These patients are very susceptible to fractures secondary to osteopenia or osteoporosis
  • Pancreatitis: This is a consequence to hypertriglyceridemia
  • Hepatic Adenomas: hepatic adenomas are common findings in older adults (in 20s-30s). Complications arising from adenomas are intrahepatic hemorrhage and malignant transformation into hepatocellular carcinoma. 

In addition to the above complications, patients with GSD Ib exhibit further complications secondary to neutrophil dysfunction. This includes recurrent infections, inflammatory bowel disease/enterocolitis, thyroid autoimmunity and hypothyroidism. [14]

Early death usually caused by acute metabolic complications (eg, hypoglycemia, acidosis), bleeding in the course of various surgical procedures (in all patients with GSD type I), and infections (in patients with GSD type Ib) is now uncommon with improving care and treatment.

Late complications, such as renal failure, hypertension, or malignant alteration of hepatic adenomas, may be responsible for mortality in adolescent and adult patients.

Long-term complications encompass growth retardation, hepatic adenomas with a high rate of malignant change, xanthomas, gout, and glomerulosclerosis. Long-term complications result from metabolic disturbances, mostly hypoglycemia. Chronic metabolic lactic acidosis and changes in the proximal renal tubule cells can lead to osteopenia and rickets with severe skeletal deformities or bone fractures, particularly of the distal extremities. Such skeletal problems seriously impair the patient's mobility. Elevated uric acid excretion along with segmental glomerular sclerosis gradually causes a decrease in the glomerular function with proteinuria, hematuria, arterial hypertension, and chronic renal failure. Because of incomplete distal tubular acidosis, a number of patients develop hypercalciuria, nephrocalcinosis, and calculosis. In a 2002 report, Mundy and Lee [35] presented the hypothesis that GSD type I and diabetes mellitus share the common mechanism for renal dysfunction. This mechanism may be due to a convergence of their metabolic sequelae in upregulation of flux through the pentose phosphate pathway that yields triose phosphate molecules, which are precursors of the lipid diacylglycerol. Diacylglycerol plays an important role in the intrarenal renin-angiotensin system via the protein kinase C pathway. Long-standing disease may be accompanied by hepatic adenomas prone to malignant alteration.

GSD type II

Aspiration pneumonia may be a complication.

In the infantile form, progressive cardiorespiratory insufficiency usually causes death by the end of the first year of life.

In the juvenile form, death is usually due to respiratory insufficiency, although a few cases have been described that were caused by the rupture of an intracranial aneurysm formed from glycogen accumulation in the smooth muscle cells of the arterial wall.

In the adult form, death due to respiratory insufficiency (eg, sleep apnea) may occur many years after the first signs of the disease have appeared.

Patients treated with enzyme replacement therapy are at risk of fractures, facial muscle weakness, dysphagia, and speech disorders. 

GSD type III

The cirrhosis found in some patients is of a mild degree and does not have a significant impact on the course of the disease. Patients can also develop hepatic adenomas which increases the risk of hepatocellular carcinoma. Muscle weakness and hypotonia is more prominent in adults with GSD IIIa, in contrast to children secondary to progression of muscle disease. Also in patients with GSD IIIa, cardiac involvement is seen in the first decade of life, usually in the form of hypertrophic cardiomyopathy and usually remains stable during the patient's life if patient is being treated appropriately. Progression to severe cardiomyopathy is less often seen but can cause severe heart failure and fatal arrhythmias (sudden death). [7]

Growth retardation may be seen in infancy and childhood, but usually reach normal levels at adolescence. Patients usually achieve normal adult height. An increased incidence of Type 2 diabetes mellitus is also being reported in patients with GSD III secondary to increased insulin resistance from constant carbohydrate enriched nutrients to induce euglycemia (same article as above). [7]

GSD type IV

In the classic form, progressive liver cirrhosis rapidly leads to hepatic insufficiency so that a fatal outcome may be expected before the end of the second year of life. Rarely, children with GSD type IV may survive longer.

Fetal hydrops and intrauterine leg contractures may be found in more severe forms.

Liver cirrhosis is not always progressive.

Moderately severe variants exist, and affected children survive longer and with predominantly muscular lesions.

GSD type VI

Serious complications are unknown.

GSD types V and VII

Renal insufficiency caused by myoglobinuria may occur. Patients with GSD type V need to take precaution with general anesthesia as it may cause acute rhabdomyolysis and myoglobinuria resulting in possible acute renal failure. [19]