Review article
DIAGNOSIS AND FOLLOW-UP OF PATIENTS WITH ANDERSON-FABRY DISEASE
VANJA BAŠIĆ KES
; Sestre milosrdnice University Hospital Centre, Department of Neurology, Referral Centre for Neuroimmunology and Neurogenetics of the Ministry of Health, Center for Anderson-Fabry Disease, Zagreb, School of Dental Medicine, University of Zagreb, Zagreb, Sc
PETAR KES
; School of Medicine, University of Zagreb, Zagreb and Academy of Medical Sciences of Croatia, Zagreb, Croatia
Abstract
Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder caused by mutations in the galactosidase (GLA) gene. Markedly reduced or absent activity of the α-galactosidase A (α-Gal A) enzyme results in progressive accumulation of glycolipids, primarily globotriaosylceramide (Gb3) in the circulation and a wide range of cells, tissues and organs, resulting in the development of a multisystem disorder. Affected patients are at a high risk of developing small-fiber neuropathy, mostly ischemic cerebrovascular stroke, chronic kidney disease, fibrotic cardiac disease resulting in rhythm and conduction disturbances, and progressive hypertrophic cardiomyopathy. Alhough the disease is X-linked, both males and females are affected. Diagnosing AFD requires high clinical suspicion, good physical examination, organ specific tests, and is confirmed by demonstrating low enzyme assays in homozygous males and gene typing in heterozygous females. Enzyme replacement therapy (ERT), oral chaperone therapy and adjunctive treatments can provide significant clinical benefit. However, much of the current literature report on outcomes after late initiation of ERT, once substantial organ damage has already occurred. In AFD patients, the success of management depends on personalized approach to care (reflecting the natural history of the specific disease phenotype), comprehensive evaluation of disease involvement prior to early ERT or chaperone initiation, and thorough routine monitoring for evidence of organ involvement in non-classic asymptomatic patients and response to therapy in treated patients. It is also very important to treat patients with adjuvant therapies for specific disease manifestations. Since AFD is a multisystem disease, the patients should be managed by an experienced multidisciplinary team. After initial evaluation, the frequency of follow-ups depends on clinical severity and involvement of different organs. The initial baseline assessment should be performed for both sexes. In women with confirmed diagnosis, organ involvement needs to be determined clinically. Asymptomatic women may be evaluated every 2 years by increasing the frequency to annual in adulthood, but symptomatic women should be monitored every 6 months, as recommended for men. Despite marked advances in patient care and improved overall outlook, there is the need for better understanding the pathogenesis of AFD and to determine appropriate age to initiate therapy in all types of patients. The need to develop more effective specific therapies was also emphasized.
Keywords
α-galactosidase A; Anderson-Fabry disease; chaperone therapy; diagnosis; enzyme replacement therapy; follow-up; globotriaosylceramide; multisystem disorder
Hrčak ID:
230812
URI
Publication date:
5.12.2019.
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