Glycogen Storage Diseases and Disorders of Gluconeogenesis

GSD I (von Gierke disease)

Most common type of GSD I: Ia (> 80%)

Onset: Before 1 year

Clinical features: Before 1 year, severe hypoglycemia, lactic acidosis, and hepatomegaly; later, hepatic adenomas, renomegaly with progressive renal insufficiency and hypertension, short stature, hypertriglyceridemia, hyperuricemia, platelet dysfunction with epistaxis, and anemia

In type Ib, less severe but includes neutropenia, neutrophil dysfunction with recurrent infections, and inflammatory bowel disease

Treatment:< 6.4 mg/dL; liver and kidney transplantation (may be successful)

For type Ib patients with neutropenia, G-CSF

Type Ia (232200*)

Glucose-6-phosphatase

Type Ib (232220*)

Glucose-6-phosphate translocase T1

Type Ic (232240*)

Glucose-6-phosphate translocase T2

Type Id (232240*)

Glucose-6-phosphate translocase T3

GSD II (Pompe disease; 232300*)

Onset: Infancy, childhood, or adulthood; residual enzyme activity in child and adult forms

Clinical features: In infantile form, cardiomyopathy with heart failure, severe hypotonia, macroglossia

In juvenile and adult forms, skeletal myopathy with delayed motor development, progressive peripheral and respiratory muscle weakness

In type IIb, intellectual disability

Treatment:

For cardiomyopathy, heart transplantation

Type IIa

Lysosomal acid alpha-glucosidase

Type IIb (Danon)

Lysosomal membrane protein-2

GSD III (Forbes disease, Cori disease, limit dextrinosis; 232400*)

Frequency: IIIa, 85%; IIIb, 15%; IIIc and IIId, rare

Onset: Infancy or childhood

Clinical features: In type IIIa, liver and muscle involvement with features of types Ia and II

In type IIIb, only liver involvement plus features of type Ia

In types IIIc and IIId, various features depending on tissue affected

Treatment: Uncooked cornstarch and continuous feeding to maintain normoglycemia, high-protein diet to stimulate gluconeogenesis

Types IIIa and IIIb

Debrancher enzyme (amyloglucosidase and oligoglucanotransferase)

Type IIIc

Amyloglucosidase only

Type IIId

Oligoglucanotransferase only

GSD IV (Andersen disease; 232500*)

Branching enzyme

Onset: Early infancy; rarely, the neonatal period, late childhood, or adulthood (manifesting as a variant nonprogressive or a neuromuscular form)

Clinical features: Hepatomegaly with progressive cirrhosis and hypoglycemia, esophageal varices, and ascites; splenomegaly; failure to thrive

In neuromuscular forms, hypotonia and muscle atrophy

Treatment: None known

For cirrhosis, liver transplantation, which treats the primary disease as well

GSD V (McArdle disease; 232600*)

Muscle phosphorylase

Onset: Adolescence or early adulthood

Clinical features: Exercise intolerance due to muscle cramps, rhabdomyolysis

Treatment: Carbohydrate administration before exercise, high-protein diet

GSD VI (Hers disease; 232700*)

Liver phosphorylase

Frequency: Rare

Onset: Early childhood

Clinical features: Benign course with symptoms lessening with aging; growth retardation, hepatomegaly, hypoglycemia, hyperlipidemia, ketosis

Treatment: Uncooked cornstarch to maintain normoglycemia

GSD VII (Tarui disease; 232800*)

Phosphofructokinase

Onset: Middle childhood

Clinical features: Exercise intolerance due to muscle cramps, rhabdomyolysis, hemolysis

Treatment: Nonspecific, avoidance of excessive exercise

GSD VIII/IX†

Onset: Heterogeneous

Clinical features: Heterogeneous; hepatomegaly, growth retardation, muscle hypotonia, hypercholesterolemia

Treatment: Nonspecific

Type IXa1 and IXa2 (306000*)

X-linked phosphorylase kinase

Type IXb (261750*)

Liver and muscle phosphorylase kinase

Type IXc (613027*)

Liver phosphorylase kinase

Type IXd (300559*)

Muscle phosphorylase kinase

GSD 0 (240600*)

Glycogen synthase

Onset: Variable but often after cessation of nighttime feedings or intercurrent illness

Clinical features: Fasting hypoglycemia and ketosis, postprandial lactic acidosis

Treatment: Frequent protein-rich meals, uncooked cornstarch at bedtime

Fanconi-Bickel syndrome (227810*)

Glucose transporter-2

Onset: Infancy

Clinical features: Failure to thrive, abdominal distention, hepatomegaly, renomegaly, mild fasting hypoglycemia and hyperlipidemia, glucose intolerance, renal Fanconi syndrome

Treatment:

Fructose 1,6-bisphosphatase deficiency (229700*)

Fructose 1,6-bisphosphatase

Onset: Infancy or early childhood

Clinical features:

Treatment:

Phosphoenolpyruvate carboxykinase deficiency (261680*)

Phosphoenolpyruvate carboxykinase

Onset: Childhood

Clinical features: Failure to thrive, hypotonia, hepatomegaly, lactic acidosis, hypoglycemia

Treatment: Avoidance of fasting, uncooked cornstarch