Fabry disease: Genetics, pathology, and treatment

Rev Assoc Med Bras (1992). 2020 Jan 13;66Suppl 1(Suppl 1):s10-s16. doi: 10.1590/1806-9282.66.S1.10.

PMID: 31939530

Thaíza Passaglia Bernardes, Renato Demarchi Foresto, Gianna Mastroianni Kirsztajn

Highlights: Genetic analysis in search of mutation for Fabry Disease is the gold standard for diagnosis, in addition to family history. It is considered that specialized treatment should begin as soon as a diagnosis is made, as this can change the disease prognosis.

Abstract

Background: Fabry disease (FD) is a X-linked recessive monogenic inheritance disorder caused by mutations in the GLA gene. Its prevalence in males is estimated to be between 1:8,454 and 1:117,000, and it is likely underdiagnosed. Mutations in the GLA gene cause progressive accumulation of globotriaosylceramide (Gb3). Gb3 accumulates in the lysosomes of several types of cells in the heart, kidneys, skin, eyes, central nervous system, and gastrointestinal system, which can result in a variety of clinical outcomes. Acroparesthesia, heat intolerance, and gastrointestinal symptoms such as nausea, vomiting, stomach discomfort, and neuropathic pain first appear in childhood. Angiokeratomas, cornea verticillata, left ventricular hypertrophy, myocardial fibrosis, proteinuria, and renal insufficiency emerge as a result of the increasing deterioration. In FD, the latter is the leading cause of death.

Objective: In addition to family history, genetic analysis in search of mutation is the gold standard for diagnosis. The enzyme activity can also be used in homozygous patients. The patient and their family should receive genetic counselling once the diagnosis has been verified. The treatment, on the other hand, currently focuses on using enzyme replacement therapy to restore the enzyme that is absent or deficient, with the goal of preventing or eliminating Gb3 deposits. Chaperones can also be deployed to help with particular cases. It is thought that specialized treatment should begin as soon as a diagnosis is made, as this can change the disease prognosis.

Keywords: Fabry disease, Alpha-Galactosidase, Chronic Renal Insufficiency, Proteinuria, Enzyme Replacement Therapy