Type	Enzyme Defect	Affected Tissue	Inheritance	Clinical Features
Ia von Gierke	Glucose-6-phosphatase	Liver; kidney	Autosomal recessive	Hypoglycemia and metabolic acidosis 3–4 h postmeal; hepatomegaly; protuberant abdomen; lordosis; elevated triglycerides; doll facies; xanthomas; impaired platelet function/bleeding; hyperuricemia; hepatic adenomas long-term
Ib von Gierke	Glucose-6-phosphate translocase	Liver	Autosomal recessive	Similar metabolic phenotype to Ia; neutropenia and recurrent infections; association with colitis (IBD-like Colitis)
Ic von Gierke	Phosphate translocase	Liver	Autosomal recessive	Similar to von Gierke; impaired insulin secretion reported
II Pompe	Alpha-1,4-glucosidase (acid maltase)	Heart; muscle; liver	Autosomal recessive	Cardiorespiratory failure and cardiomyopathy; infantile, juvenile, or adult forms with muscle weakness and respiratory compromise
IIIa-b Cori aka Forbes Disease	Debranching enzyme(s)	Liver; muscle; heart (IIIb is liver only)	Autosomal recessive	Milder than GSD I; tolerate longer fasting; variable hypoglycemia; hepatomegaly; growth failure; hepatic fibrosis; ↑ transaminases; lactic acid and uric acid usually normal
IV Andersen Disease	Branching enzyme (α-1,4-glucan 6-glucosyltransferase)	Liver	Autosomal recessive	Progressive liver cirrhosis 3–15 months; failure to thrive; abdominal distention; hepatosplenomegaly**; no hypoglycemia until end-stage liver disease
VI Hers Disease	Liver glycogen phosphorylase (Hers)	Liver	Autosomal recessive	Hepatomegaly; growth retardation; microsteatosis; hypoglycemia with prolonged fasting; noted in Mennonite community
IX (alpha)	Liver phosphorylase kinase	Liver; muscle	X-linked recessive or autosomal recessive	Presentation 1–5 years; hepatomegaly; growth retardation; motor delay; hypotonia; ↑ transaminases, cholesterol, lipids; fasting hyperketosis and hypoglycemia
XI	GLUT2 transporter defect	Liver; kidney	Autosomal recessive	Hepatomegaly; hypergalactosemia; postprandial hyperglycemia; hyperlipidemia and hypercholesterolemia; hypophosphatemic rickets; moon facies

Glycogen Storage Disease

Overview

Glycogen storage diseases are inherited defects of enzymes or transporters in glycogen metabolism that cause abnormal glycogen accumulation and/or impaired glucose mobilization, producing organ dysfunction and metabolic disturbances.

Classification and Clinical Patterns

Classic types: Historically a set of roughly a dozen well characterized types, each linked to a specific enzyme or transporter defect.
Clinical groups: Primarily hepatic forms; primarily myopathic forms; mixed hepatic and myopathic forms.
Examples:

Types I, IIIb, IV, VI, IX, and XI commonly present with predominant liver disease
Types II and IIIa have mixed hepatic and muscle involvement.

Prenatal Diagnosis

When a familial pathogenic variant is known, many GSDs can be diagnosed prenatally or by targeted prenatal genetic testing; the ability to detect a specific subtype prenatally depends on identification of the causal mutation and access to appropriate testing.

Diagnostic Approach

Molecular testing: Gene sequencing and targeted mutation analysis are the preferred confirmatory tests when available.
Biochemical and histologic testing: Enzyme activity assays on liver, muscle, or cultured cells and characteristic histopathology support diagnosis when genetics are inconclusive or not available.

Inheritance

Most classical glycogen storage diseases are autosomal recessive; the common alpha subunit form of GSD IX is X‑linked and other variations in inheritance exist for specific subtypes.

Clinical Importance

Early and accurate diagnosis permits targeted dietary therapy, medical management, surveillance for complications, genetic counseling, and interventions that reduce organ damage and improve survival.

Notes:
### Glycogen Storage Disease
Glycogen storage diseases (GSDs) are inherited disorders caused by deficiencies of specific enzymes or transporters in glycogen metabolism that lead to abnormal glycogen accumulation and/or impaired glucose mobilization. Early recognition and diagnosis are critical to prevent organ injury and improve long‑term outcomes.

#### Key points
- **Etiology:** Caused by pathogenic variants affecting enzymes or transport proteins in glycogen synthesis, branching, debranching, breakdown, or glucose export from hepatocytes.
- **Classification:** Historically described as a set of roughly a dozen classical types with distinct enzyme defects and clinical syndromes; clinical categories include primarily hepatic forms, primarily myopathic forms, and mixed forms.
- **Primarily hepatic types:** I, IIIb, IV, VI, IX, and XI.
- **Mixed hepatic and myopathic types:** II and IIIa.
- **Prenatal diagnosis:** When a familial pathogenic variant is known, many GSDs can be identified prenatally or by prenatal genetic testing; feasibility depends on known mutation status and testing availability.
- **Diagnosis:** Confirmed by molecular genetic testing when possible; specialized biochemical testing such as enzyme activity assays on liver, muscle, or cultured fibroblasts and targeted histopathology remain important when genetic testing is unavailable or inconclusive.
- **Inheritance:** Most classical GSDs are autosomal recessive; an important exception is the common X‑linked form of GSD IX affecting the alpha subunit of phosphorylase kinase, which is X‑linked.
- **Clinical importance:** Early, accurate diagnosis enables targeted dietary and medical therapy, surveillance for organ complications, genetic counseling, and when appropriate, timely definitive interventions to reduce morbidity and mortality.