Fabry Disease 2012

Summary

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Phenotype

Built up Gb3 and glycosphingolipids may lead to heart attack and stroke

As almost each family has its own private mutation, phenotypes of affected persons can be very variable. In general, with increasing age symptoms become more severe. This effect is due to more and more accumulated glycosphingolipids that cannot be converted by the dysfunctional enzyme. The built up globotriaoslyceramide (Gb3) and related glycosphingolipids in the lysosomes, tissues, blood vessels and organs lead to a malfunction of major organs in the body starting at an age of 30 - 35 (see picture on the right). Thus untreated patients die approximately 10 - 20 years early (females and males, respectively).

Symptoms (onset)

Childhood

• Acroparesthesia (Numbness in extremities)
• Hypohidrosis (decreased sweating)
• Cornea opacity

Adolesence

• Gastro Intestinal Manifestation (nausea, vomitting)
• Angiokeratoma
• Depression
• Heat/cold intolerance
• Fatigue

Adulthood

• Renal Disease
  • Progressive renal insufficiency
  • End-stage renal disease
• Cardiac Disease
  • Hypertension (high blood pressure)
  • Cardiomyopathy
• Central Nervous System Disease
  • Headache
  • Stroke
  • Ischaemic cerebrovascular events
  • Binswanger’s Disease (Vascular dementia)

Cross-references

• HGMD
• KEGG Disease
• OMIM
• Wikipedia
• Fabry Registry
• NCBI Bookshelf, Fabry Disease, A. Mehta and D. Hughes

Biochemical disease mechanism

Cross-references

• KEGG
• MetaCyc
• PDB

Mutations

Reference sequence

Reference Sequence of α-galactosidase A from Uniprot entry P06280

>gi|4504009|ref|NP_000160.1| alpha-galactosidase A precursor [Homo sapiens]
MQLRNPELHLGCALALRFLALVSWDIPGARALDNGLARTPTMGWLHWERFMCNLDCQEEPDSCISEKLFM
EMAELMVSEGWKDAGYEYLCIDDCWMAPQRDSEGRLQADPQRFPHGIRQLANYVHSKGLKLGIYADVGNK
TCAGFPGSFGYYDIDAQTFADWGVDLLKFDGCYCDSLENLADGYKHMSLALNRTGRSIVYSCEWPLYMWP
FQKPNYTEIRQYCNHWRNFADIDDSWKSIKSILDWTSFNQERIVDVAGPGGWNDPDMLVIGNFGLSWNQQ
VTQMALWAIMAAPLFMSNDLRHISPQAKALLQDKDVIAINQDPLGKQGYQLRQGDNFEVWERPLSGLAWA
VAMINRQEIGGPRSYTIAVASLGKGVACNPACFITQLLPVKRKLGFYEWTSRLRSHINPTGTVLLQLENT
MQMSLKDLL