For more information, see table .
See also Approach to the Patient With a Suspected Inherited Disorder of Metabolism Approach to the Patient With a Suspected Inherited Disorder of Metabolism Most inherited disorders of metabolism (inborn errors of metabolism) are rare, and therefore their diagnosis requires a high index of suspicion. Timely diagnosis leads to early treatment and... read more .
Fabry disease is an X-linked X-Linked Recessive Genetic disorders determined by a single gene (Mendelian disorders) are easiest to analyze and the most well understood. If expression of a trait requires only one copy of a gene (one allele)... read more deficiency of the lysosomal enzyme alpha-galactosidase A, which is needed for normal trihexosylceramide catabolism. Glycolipid (globotriaosylceramide) accumulates in many tissues (eg, vascular endothelium, lymph vessels, heart, kidney).
Diagnosis of Fabry Disease
Clinical evaluation
Enzyme analysis
Sometimes DNA analysis
Diagnosis in males is by enzyme analysis and is clinical based on appearance of typical skin lesions (angiokeratomas) over the lower trunk and by characteristic features of peripheral neuropathy (causing recurrent burning pain in the extremities), corneal opacities, and recurrent febrile episodes. Death results from renal failure or cardiac or cerebral complications of hypertension or other vascular disease.
Heterozygous females are usually asymptomatic but may have an attenuated form of disease often characterized by corneal opacities.
Diagnosis of Fabry disease is by DNA analysis (especially in females) and/or assay of galactosidase activity—prenatally in amniocytes or chorionic villi and postnatally in serum or white blood cells. (See also testing for suspected inherited disorders of metabolism Initial testing Most inherited disorders of metabolism (inborn errors of metabolism) are rare, and therefore their diagnosis requires a high index of suspicion. Timely diagnosis leads to early treatment and... read more .)
Treatment of Fabry Disease
Enzyme replacement
Sometimes migalastat
Treatment is enzyme replacement with recombinant alpha-galactosidase A (agalsidase alpha or agalsidase beta) combined with supportive measures for fever and pain (1 Treatment reference Fabry disease is a sphingolipidosis, an inherited disorder of metabolism, caused by deficiency of alpha-galactosidase A, which causes angiokeratomas, acroparesthesias, corneal opacities, recurrent... read more ).
Migalastat, an oral pharmacologic chaperone that binds to and stabilizes specific mutant forms of alpha-galactosidase, is used as an alternative in some patients.
Kidney transplantation is effective for treating renal failure.
Treatment reference
1. Germain DP, Altarescu G, Barriales-Villa R, et al. An expert consensus on practical clinical recommendations and guidance for patients with classic Fabry disease. Mol Genet Metab. 2022;137(1-2):49-61. doi:10.1016/j.ymgme.2022.07.010
More Information
The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.
Online Mendelian Inheritance in Man (OMIM) database: Complete gene, molecular, and chromosomal location information
Drugs Mentioned In This Article
Drug Name | Select Trade |
---|---|
migalastat |
Galafold |
alpha-galactosidase |
Beano, Beano Meltaways, Beano To Go, Gas-X Prevention |
agalsidase beta |
Fabrazyme |