White matter lesions in Fabry disease before and after enzyme replacement therapy: a 2-year follow-up

Abstract

-Purpose: To report the clinical and neuroimaging, central nervous system (CNS) findings of patients with Fabry disease (FD) during 24 months of enzyme replacement therapy (ERT) with agalsidasealpha. Method: Eight patients were included. Six completed 24 months of ERT. Clinical and magnetic resonance imaging (MRI) data were obtained at 0, 12 and 24 months of ERT. White matter lesions (WML) were evaluated as well as their relation to age, symptoms and neurological examination (CNS score). Results: MRI was stable in 3 patients. WML and CNS score worsened in one patient, fluctuated in another, and improved in the sixth patient. In the whole series, there were 15 WML at baseline, and 19 at the 24 th month. In two years, 4 lesions disappeared, whereas 8 appeared. Conclusion: A widespread pattern of silent WML in FD was seen. In two years, some WML appeared, and some disappeared. If these phenomena were related to the natural history, remains to be demonstrated.KEY WORDS: Fabry disease, enzyme-replacement therapy, magnetic resonance imaging, alpha-galactosidase A, white matter lesion.Lesões da substância branca na doença de Fabry antes e depois da terapia de reposição enzimática : um seguimento de 2 anos RESUMO -Objetivo: Relatar os achados neurológicos e de imagem do sistema nervoso central (SNC), observados durante 24 meses de tratamento de reposição enzimática (ERT) com agalsidase-alfa, em pacientes com a doença de Fabry (FD). Método: 8 pacientes foram incluídos; 6 completaram 24 meses de ERT. Os dados foram obtidos aos 0, 12 e 24 meses de ERT. Lesões de substância branca (WML) foram avaliadas assim como sua relação com a idade e o exame neurológico (escore SNC). Resultados: Os achados de ressonân-cia nuclear magnética foram estáveis em 3 pacientes. As WML e o escore SNC pioraram em um caso; flutuaram em um outro caso; e melhoraram no sexto paciente. No todo, havia 15 WML antes da ERT e 19 WML depois de 24 meses de ERT. Em dois anos, 4 lesões desapareceram e 8 novas surgiram. Conclusões: Viu-se um padrão difuso de WML assintomáticas, na FD. Em dois anos, algumas WML surgiram, enquanto outras desapareceram. Resta demonstrar se esses fenômenos fazem parte da história natural da doença. PALAVRAS-CHAVE: doença de Fabry, terapia de reposição enzimática, ressonância nuclear magnética, alfagalactosidase A, lesões de substância branca.Fabry disease (FD) is an X-linked disorder resulting from a mutation of the α-galactosidase A gene at Xq22. The gene defect causes a very low specific activity of the enzyme α-galactosidase (α-Gal A) (NM_000169), which leads to a progressive lysosomal deposition of globotriaosylceramide (GL-3) in vascular endothelium and smooth muscle cells, myocardium, renal epithelium, and the central nervous sys-

Amelioration of white-matter lesions in a patient with Fabry disease

“…The disappearance of small WMLs after 24 months of ERT has been reported in a 24-year-old patient who had only 2 small lesions before ERT [7]. Although the apparent disappearance of such small lesions can be attributed to slice gaps on MRI, the widespread WMLs in our patient were visible on multiple slices (Fig.…”

Kidney Function and 24-Hour Proteinuria in Patients with Fabry Disease during 36 Months of Agalsidase Alfa Enzyme Replacement Therapy: A Brazilian Experience

“…[2] There were no cases of hypertensive disorder, smoking, hyperlipidemia, or other chronic diseases. Neurologic and molecular characteristics of this population have already been published [20][21][22][23] and are summarized in Table 1.…”

Agalsidase alfa for the treatment of fabry disease: a closer look

“…The clinical efficacy of Replagal has been studied in six randomized clinical trials [41,[50][51][52][53][54], fourteen open-label studies [15,[36][37][38][42][43][52][53][55][56][57][58][59][60], and a few descriptive studies [21,[61][62]. Data extracted from the Fabry Outcome Survey (FOS) has provided additional information on the effects of Replagal [20,[63][64][65][66][67][68][69][70][71][72].…”