[Fabry disease in light of recent review].

Fabry disease is a lysosomal storage disorder that is caused by mutations in the gene encoding a-galactosidase A on Xq22.1. Typically hemizygous male patients exhibit classic phenotypes such as angiokeratoma, acroparesthesias, episodic pain "crises," hypohidrosis, and whorl-shaped corneal opacities from childhood. However, during adulthood, they gradually develop kidney failure, heart disease, and strokes resulting in early death between 40 to 50 years of age. However, recent studies have indicated a high prevalence of disabling clinical symptoms in heterozygous females patients. Patients having the cardiac variant of Fabry's disease exhibit only left ventricular hypertrophy, while patients having the renal variant exhibit only kidney failure. Individuals affected by these variants show higher residual enzyme activity of alpha-galactosidase A than individuals affected by the classic form of Fabry's disease due to missense mutations of the GLA gene. The cerebrovascular involvement in Fabry disease is not rare in both adult hemizygotes and heterozygotes. Infarctions caused by the occulsion of small vessels involving mostly the vertebrobasilar region in approximately two-thirds of the cases, and that is associated with the deposition glycoshingolipids including GL-3 in the walls of these vessels. In Caucasian patients, elongated, ectatic, and tortuous vertebral and basilar arteries are frequently observed on MRAs. Life-threatening megadolichobasilar anomaly with thrombosis has been identified in a large Hungarian family in which the family members share L16P mutation. On performing MRI, an increased signal intensity was observed in the pulvinar in T1-weighted images; this is the characteristic so-called "pulvinar sign". Enzyme replacement therapy has been approved in Japan since 2004 and 2007 for agalsidase beta and agalsidase alpha, respectively. This treatment modestly improves the small-fiber neuropathy, hypohidrosis, hypertrophic cardiomyopathy, and stabilizes the renal function in the long term for up to 54 months. However, it has not helped in decreasing the incidence of strokes.
AuthorsEiichiro Uyama
JournalBrain and nerve = Shinkei kenkyū no shinpo (Brain Nerve) Vol. 60 Issue 11 Pg. 1235-44 (Nov 2008) ISSN: 1881-6096 [Print] Japan
PMID19069157 (Publication Type: English Abstract, Journal Article, Review)
Chemical References
  • Isoenzymes
  • agalsidase alfa
  • agalsidase beta
  • alpha-Galactosidase
  • Adult
  • Cerebral Infarction (etiology)
  • Chromosomes, Human, X (genetics)
  • Fabry Disease (classification, diagnosis, genetics, therapy)
  • Female
  • Genotype
  • Humans
  • Isoenzymes (administration & dosage)
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Mutation, Missense
  • alpha-Galactosidase (administration & dosage, genetics)

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