Fabry disease: a review of current management strategies

Abstract

Fabry disease is an X-linked inherited condition due to the absence or reduction of alpha-galactosidase activity in lysosomes, that results in accumulation of globotriaosylceramide (Gb3) and related neutral glycosphingolipids. Manifestations of Fabry disease include serious and progressive impairment of renal and cardiac function. In addition, patients experience pain, gastrointestinal disturbance, transient ischaemic attacks and strokes. Additional effects on the skin, eyes, ears, lungs and bones are often seen. The first symptoms of classic Fabry disease usually appear in childhood. Despite being X-linked, females can suffer the same severity of symptoms as males, and life expectancy is reduced in both females and males. Enzyme replacement therapy (ERT) can stabilize the progression of the disease. The rarity of the classic form of Fabry disease, however, means that there is a need to improve the knowledge and understanding that the majority of physicians have concerning Fabry disease, in order to avoid misdiagnosis and/or delayed diagnosis. This review aims to raise awareness of the signs and symptoms of Fabry disease; to provide a general diagnostic algorithm and to give an overview of the effects of ERT and concomitant treatments. We highlight a need to develop comprehensive international guidelines to optimize ERT and adjunctive therapy in patients with Fabry disease, including females and children.

Fabry Liga: Klinikinis Atvejis Ir Literatūros Apžvalga

“…Klasikinio fenotipo atveju homozigotiniams vyrams, turintiems alfa-galaktozidazės A trūkumą, nustatomi tipiški ligos simptomai (2 lentelė) [17]: nervų pažeidimas (skausmas), odos pažeidimas (angiokeratoma), inkstų (proteinurija, inkstų nepakankamumas), šir-dies ir kraujagyslių sistemos pažeidimas (kardiomiopatija, aritmijos), kochleovestibulinio aparato ir smegenų kraujagyslių pažeidimas (praeinantis smegenų išemijos priepuolis, insultas). Heterozigotinėms moterims Fabry liga gali pasireikšti nuo labai lengvų iki sunkių požymių [18].…”

Clinical manifestations and treatment of Anderson-Fabry disease in a middle age man (RCD code: III-2B.2a)

“…Alpha-galactosidase enzyme activity for females may remain within normal limits, therefore in case of suspicion, molecular genetic test should be carried out to confirm the diagnosis. After identification of a new patient, there is a chance to diagnose five Fabry disease cases in the same family [8].…”

“…ERT reduces Gb3 accumulation in the tissues, thus protecting against the disease complications and stabilize the progression of the disease [8]. There are two different kinds of alfa galaktozidase A enzyme products available: agalsidase alfa and agalsidase beta.…”

Nanocarriers for Cytosolic Drug and Gene Delivery in Cancer Therapy

“…Thus, targeting of degradative enzymes to lysosomes would result in reversing of those disease conditions. For example, enzyme replacement therapy with agalsidase alpha which is an exogenous source of -galactosidase A is proved to be effective in treatment of Fabry's disease (Mehta et al, 2010).…”