Alpha-galactosidase deficiency (Fabry disease, Fabry syndrome, Anderson-Fabry syndrome) is caused by gene variations that result in deficiency in lysosomal alpha-galactosidase.
Leads to an excess of glycosphyngolipids (globotriaosylceramide, Gal-Gal-Glc-Cer) in the lysosomes of various tissues and organs. Clinical symptoms are related to heart, skin, kidneys and nervous system.
The full syndrome has:
- Characteristic skin lesions (angiokeratomas, purpura papulosa haemorrhagica Hebrae) over the lower trunk but can be absent
- Corneal deposits (corneal verticillata, Fleischer vortex dystrophy, whorl-like corneal dystrophy)
- Febrile episodes
- Burning pain in the extremities due to small-fiber peripheral neuropathy.
- Early death from renal failure and cardiac or cerebral complications of hypertension
- Possibly short PR interval (prediposes to potentially malignant arrhthmias)
- Possibly mitral valve prolapse
- Possibly high frequency sensorineural deafness or tinnitus
- Possibly hypohidrosis or anhidrosis with associated heat intolerance
Residual enzyme function results in a cardiac form manifesting about 60 years of age with:
- Left ventricular hypertrophy
- Sometimes renal failure
If heterozygous may have an attenuated form
- Corneal opacities commoner than in males
Attenuated forms which are likely to be underdiagnosed can present with:
- Decreased alpha-galactosidase activity in urine and plasma.
- Genetic testing
- Agalsidase beta
- Agalsidase alpha (may not be as effective from switch studies)
- Pharmacological chaperones may help with specific mutations but do not appear to be a general solution. Migalastat was the first to reach the market.
- ↑ Linthorst GE, De Rie MA, Tjiam KH, Aerts JM, Dingemans KP, Hollak CE. Misdiagnosis of Fabry disease: importance of biochemical confirmation of clinical or pathological suspicion. The British journal of dermatology. 2004 Mar; 150(3):575-7.(Link to article – subscription may be required.)
- ↑ Rolfs A, Böttcher T, Zschiesche M, Morris P, Winchester B, Bauer P, Walter U, Mix E, Löhr M, Harzer K, Strauss U, Pahnke J, Grossmann A, Benecke R. Prevalence of Fabry disease in patients with cryptogenic stroke: a prospective study. Lancet. 2005 Nov 19; 366(9499):1794-6.(Link to article – subscription may be required.)
- ↑ Smid BE, Rombach SM, Aerts JM, Kuiper S, Mirzaian M, Overkleeft HS, Poorthuis BJ, Hollak CE, Groener JE, Linthorst GE. Consequences of a global enzyme shortage of agalsidase beta in adult Dutch Fabry patients. Orphanet journal of rare diseases. 2011; 6:69.(Epub) (Link to article – subscription may be required.)