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glycogen storage disease type 3

MIM.232400 1p21

Thursday 9 February 2006

Definition: Autosomal recessive metabolic disease. Glycogen storage disease III (GSD3) is caused by mutation in the gene encoding the glycogen debrancher enzyme (AGL; MIM.610860).

Glycogen storage disease III is an autosomal recessive metabolic disorder caused by deficiency of the glycogen debrancher enzyme and associated with an accumulation of abnormal glycogen with short outer chains.

Most patients are enzyme-deficient in both liver and muscle (IIIa), but about 15% are enzyme-deficient in liver only (IIIb).

These subtypes have been explained by differences in tissue expression of the deficient enzyme.

In rare cases, selective loss of only 1 of the 2 debranching activities, glucosidase or transferase, results in type IIIc or IIId, respectively.

Clinically, patients with GSD III present in infancy or early childhood with hepatomegaly, hypoglycemia, and growth retardation.

Muscle weakness in those with IIIa is minimal in childhood but can become more severe in adults; some patients develop cardiomyopathy.

Digital slides

- Case 34 : glycogen storage disease type 3 (GSD3)
- Case 46 : glycogen storage disease type 3 (GSD3)
- Case 247 : glycogen storage disease type 3 (GSD3)

Synopsis

- short stature
- growth retardation

- carniofacial anomalies

  • midface hypoplasia
  • deep-set eyes
  • depressed nasal bridge
  • broad upturned nasal tip
  • bow-shaped lips
    - thin vermillion border

- cardiac anomalies

  • cardiomyopathy
  • ventricular hypertrophy on ECG

- hepatic anomalies

  • hepatomegaly
  • hepatic fibrosis
  • glycogen hepatocytic overload
  • rarefied cytoplasm
  • pyknotic anc eccentrically-located nuclei
  • mosaic appearance
  • hepatocytic steaosis
  • hepatocyte vacuolation
  • cirrhosis (adults)
  • hepatic tumors
    • hepatic adenoma
    • hepatocellualr carcinoma (adults)

- muscle weakness (increases with age)
- distal muscle wasting
- myopathy
- hypoglycemia

Laboratory

- amylo-1,6-glucosidase deficiency
- hypoglycemia
- hyperlipidemia
- normal blood lactate
- normal uric acid
- elevated transaminases

Electron microscopy

- peripheral blood leucocytes: excess glycogen

Subtypes

- glycogenosis type 3a (GSD3a or GSD type IIIa): both liver and muscle involvement
- glycogenosis type 3b (GSD3b or GSD type IIIb): liver involvement only (15% of all cases)

Etiology

- germline mutations in the amylo-1,6-glucosidase, 4-alpha-glucoanotransferase gene (AGL) (MIM.232400)

References

- Fellows IW, Lowe JS, Ogilvie AL, Stevens A, Toghill PJ, Atkinson M. Type III glycogenosis presenting as liver disease in adults with atypical histological features. J Clin Pathol. 1983 Apr;36(4):431-4. PMID: #6572629#