Difference between revisions of "Glycogen storage diseases"

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=Specific diseases=
=Specific diseases=
==Pompe disease==
==Pompe disease==
*[[AKA]] glycogenosis II, [[AKA]] acid maltase deficiency, [[AKA]] alpha-1,4-glucosidase deficiency.<ref>URL: [http://www.ncbi.nlm.nih.gov/omim/606800 http://www.ncbi.nlm.nih.gov/omim/606800]. Accessed on: 11 January 2011.</ref>
*[[AKA]] glycogen storage disease type II, [[AKA]] acid maltase deficiency, [[AKA]] alpha-1,4-glucosidase deficiency.<ref>URL: [http://www.ncbi.nlm.nih.gov/omim/606800 http://www.ncbi.nlm.nih.gov/omim/606800]. Accessed on: 11 January 2011.</ref>
 
===General===
===General===
Deficiency of ''alpha-1,4-glucosidase''; it degrades glycogen to glucose in lysosomes.
*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.<ref>Pompe J-C. Over idiopatische hypertropie van het hart. Ned Tijdscr Geneeskd 1932; 76:304.</ref>
* A enzyme replacement therapy exists. <ref>{{Cite journal  | last1 = Amalfitano | first1 = A. | last2 = Bengur | first2 = AR. | last3 = Morse | first3 = RP. | last4 = Majure | first4 = JM. | last5 = Case | first5 = LE. | last6 = Veerling | first6 = DL. | last7 = Mackey | first7 = J. | last8 = Kishnani | first8 = P. | last9 = Smith | first9 = W. | title = Recombinant human acid alpha-glucosidase enzyme therapy for infantile glycogen storage disease type II: results of a phase I/II clinical trial. | journal = Genet Med | volume = 3 | issue = 2 | pages = 132-8 | month =  | year =  | doi = 10.109700125817-200103000-00007 | PMID = 11286229 }}
</ref>
 
===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.


Clinical:
Note: clinical course correlates with remaining enzyme activity.<ref>{{Cite journal  | last1 = Hermans | first1 = MM. | last2 = van Leenen | first2 = D. | last3 = Kroos | first3 = MA. | last4 = Beesley | first4 = CE. | last5 = Van Der Ploeg | first5 = AT. | last6 = Sakuraba | first6 = H. | last7 = Wevers | first7 = R. | last8 = Kleijer | first8 = W. | last9 = Michelakakis | first9 = H. | title = Twenty-two novel mutations in the lysosomal alpha-glucosidase gene (GAA) underscore the genotype-phenotype correlation in glycogen storage disease type II. | journal = Hum Mutat | volume = 23 | issue = 1 | pages = 47-56 | month = Jan | year = 2004 | doi = 10.1002/humu.10286 | PMID = 14695532 }}</ref>
*Floppy baby.  
*Big heart.  
**Often early death from cardiac failure.


===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.
<gallery>
<gallery>
File:Pompe_vacuoles.jpg | Large vacuoles in Pompe disease (H&E, WC/jensflorian)
File:Pompe_vacuoles.jpg | Large vacuoles in Pompe disease (H&E, WC/jensflorian)

Latest revision as of 12:24, 17 April 2015

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:

  • Abnormal glycogen is not easy to spot in this muscle biopsy HE stain (WC/jensflorian)

  • Intramuscular glycogen is usually PAS+++ve (WC/jensflorian)

  • Lack of staining in intramuscular deposits, Trichrom Gömöri (WC/jensflorian)

  • Lafora-like polyglucosan bodies in the CNS, low magnification (WC/jensflorian)

  • Lafora-like polyglucosan bodies in the CNS, higher magnification(WC/marvin101)

  • Large vacuoles in the liver, HE stain (WC/Netha Hussain)

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.

  • Large vacuoles in Pompe disease (H&E, WC/jensflorian)

  • Clinical phenotype in Pompe disease (WC/Wens et. al.)

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.
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