Glycogen storage diseases

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Glycogen storage diseases a group of diseases characterized by the accumulation of glycogen.

Clinical picture

  • Exercise intolerance
  • Usually due to specific muscle enzyme defects

DDx:

  • Mitochondriopathies
  • Carnitine palmitoyltransferase II (CPT2) deficiency

General microscopic

Features:[1]

  • +/-Vacuolated muscle fibres.
  • acid phosphatase+ve in vaculoes.
  • PAS+ve.

Images:

Electron microscopy

  • Electron dense deposits.

Specific diseases

Pompe disease

  • AKA glycogen storage disease type II, AKA acid maltase deficiency, AKA alpha-1,4-glucosidase deficiency.[2]

General

  • Deficiency of alpha-1,4-glucosidase; it degrades glycogen to glucose in lysosomes.
  • Autosomal recessive inheritance.
  • Identified in 1932 by dutch pathologist Johannes C. Pompe.[3]
  • A enzyme replacement therapy exists. [4]

Clinical

  • infantile onset (usually at age 4-8months):
    • Floppy baby.
    • Macroglossia.
    • Hepatomegaly.
    • Big heart - often early death from cardiac failure.
  • late onset (usually at age 1-2years):
    • Progressive muscle weakness (myopathy).
    • Usually only mild cardiac involvement.

Note: clinical course correlates with remaining enzyme activity.[5]

Diagnosis

  • Mutations in acid alpha-glucosidase.
  • Elevated serum CK (<10x).
  • Cytoplasmic (lysosomal) vacuoles (Acid phosphatase +ve).
  • Muscle fibers with vacuoles enlarged.
  • Type 1 fibers more often affected.
  • PAS+ve deposits.
  • Autophagic (Lysosomal) vacuoles in electron microscopy.

Cori disease

  • AKA glycogen storage disease type III.[6]

General

  • Hepatomegaly.

Microscopic

Features:

  • Hypertrophic hepatocytes with pale cytoplasm.
    • Classically: PAS +ve, PAS-D -ve.
  • Portal fibrosis.

Image:

Stains

See also

References

  1. URL: http://neuromuscular.wustl.edu/pathol/acidmchi.htm. Accessed on: 11 January 2011.
  2. URL: http://www.ncbi.nlm.nih.gov/omim/606800. Accessed on: 11 January 2011.
  3. Pompe J-C. Over idiopatische hypertropie van het hart. Ned Tijdscr Geneeskd 1932; 76:304.
  4. Amalfitano, A.; Bengur, AR.; Morse, RP.; Majure, JM.; Case, LE.; Veerling, DL.; Mackey, J.; Kishnani, P. et al. "Recombinant human acid alpha-glucosidase enzyme therapy for infantile glycogen storage disease type II: results of a phase I/II clinical trial.". Genet Med 3 (2): 132-8. doi:10.109700125817-200103000-00007. PMID 11286229.
  5. Hermans, MM.; van Leenen, D.; Kroos, MA.; Beesley, CE.; Van Der Ploeg, AT.; Sakuraba, H.; Wevers, R.; Kleijer, W. et al. (Jan 2004). "Twenty-two novel mutations in the lysosomal alpha-glucosidase gene (GAA) underscore the genotype-phenotype correlation in glycogen storage disease type II.". Hum Mutat 23 (1): 47-56. doi:10.1002/humu.10286. PMID 14695532.
  6. URL: http://www.ncbi.nlm.nih.gov/omim/232400. Accessed on: 25 January 2011.