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'''Glycogen storage | '''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:<ref>URL: [http://neuromuscular.wustl.edu/pathol/acidmchi.htm http://neuromuscular.wustl.edu/pathol/acidmchi.htm]. Accessed on: 11 January 2011.</ref> | Features:<ref>URL: [http://neuromuscular.wustl.edu/pathol/acidmchi.htm http://neuromuscular.wustl.edu/pathol/acidmchi.htm]. Accessed on: 11 January 2011.</ref> | ||
*+/-Vacuolated muscle fibres. | *+/-Vacuolated muscle fibres. | ||
*acid phosphatase+ve in vaculoes. | |||
*PAS+ve. | |||
Images: | Images: | ||
<gallery> | |||
File:HE_glycogen_storage_disease_highmag.jpg | Abnormal glycogen is not easy to spot in this muscle biopsy HE stain (WC/jensflorian) | |||
File:PAS_glycogen_storage_disease_intermed_mag.jpg | Intramuscular glycogen is usually PAS+++ve (WC/jensflorian) | |||
Trichrom_glycogen_storage_disease_intermed_mag..jpg | Lack of staining in intramuscular deposits, Trichrom Gömöri (WC/jensflorian) | |||
File:Polyglucosan body disease.jpg | Lafora-like polyglucosan bodies in the CNS, low magnification (WC/jensflorian) | |||
File:Adult polyglucosan body disease histopathology.jpg | Lafora-like polyglucosan bodies in the CNS, higher magnification(WC/marvin101) | |||
File:Glycogen storage disorder - Liver.jpg | Large vacuoles in the liver, HE stain (WC/Netha Hussain) | |||
</gallery> | |||
*[http://neuromuscular.wustl.edu/pathol/acidmalt.htm Glycogen storage disease (wustl.edu)]. | *[http://neuromuscular.wustl.edu/pathol/acidmalt.htm Glycogen storage disease (wustl.edu)]. | ||
*[http://www.brown.edu/Courses/Digital_Path/systemic_path/hepatobiliary/gsd1.html Glycogen storage disease (brown.edu)]. | |||
=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.<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=== | |||
*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. | |||
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> | |||
===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> | |||
File:Pompe_vacuoles.jpg | Large vacuoles in Pompe disease (H&E, WC/jensflorian) | |||
File:Phenotypical-variation-within-22-families-with-Pompe-disease-1750-1172-8-182-S1.ogv | Clinical phenotype in Pompe disease (WC/Wens et. al.) | |||
</gallery> | |||
==Cori disease== | |||
*[[AKA]] glycogen storage disease type III.<ref>URL: [http://www.ncbi.nlm.nih.gov/omim/232400 http://www.ncbi.nlm.nih.gov/omim/232400]. Accessed on: 25 January 2011.</ref> | |||
===General=== | |||
*Hepatomegaly. | |||
===Microscopic=== | |||
Features: | |||
*Hypertrophic hepatocytes with pale cytoplasm. | |||
**Classically: PAS +ve, PAS-D -ve. | |||
*Portal fibrosis. | |||
Image: | |||
*[http://commons.wikimedia.org/wiki/File:Glycogen_storage_disease_in_liver_-_high_mag.jpg Glycogen storage disease consistent with Cori disease - high mag. (WC)]. | |||
==Stains== | ==Stains== | ||
| Line 12: | Line 84: | ||
*[[PAS-D stain|PAS-D]] -ve. | *[[PAS-D stain|PAS-D]] -ve. | ||
==References | =See also= | ||
*[[Lysosomal storage diseases]]. | |||
=References= | |||
{{Reflist|2}} | {{Reflist|2}} | ||
[[Category:Weird stuff]] | [[Category:Weird stuff]] | ||