Clinical manifestations of Fabry disease in children: Data from the Fabry Outcome Survey

TLDR

Fabry disease is a rare X‑linked lysosomal storage disorder caused by alpha‑galactosidase A deficiency, leading to globotriaosylceramide accumulation, organ failure, and premature death. This study reports the clinical manifestations of Fabry disease in children enrolled in the European Fabry Outcome Survey (FOS). Baseline demographic and clinical data were analyzed for 82 children (40 boys, 42 girls) under 18 years of age in the FOS database. Median age at evaluation was 12.5 y for boys and 13.2 y for girls; about 80 % had neurological symptoms, 60 % gastrointestinal symptoms, over 40 % had tinnitus, vertigo, fatigue or angiokeratoma, with symptoms appearing in early childhood, similar in frequency between sexes but 2–5 years later in girls, a 3‑year diagnostic delay, frequent misdiagnosis, and no life‑threatening complications yet, indicating common symptoms that may affect quality of life.

Abstract

Fabry disease is a rare X-linked disorder caused by deficient activity of the enzyme alpha-galactosidase A. This produces progressive lysosomal accumulation of globotriaosylceramide throughout the body, leading to organ failure and premature death.Here, we present the clinical manifestations of Fabry disease in children enrolled in FOS--the Fabry Outcome Survey--a European database of the natural history of Fabry disease and the effects of enzyme replacement therapy with agalsidase alfa (Replagal).Currently, there are 545 patients in FOS, from 11 European countries. We analysed the baseline demographic and clinical characteristics of 82 of these patients (40 boys, 42 girls) who were below 18 y of age. The median age at evaluation (defined as the median age at entry into FOS) was 12.5 and 13.2 y for boys and girls, respectively.The most frequent early clinical manifestations of Fabry disease were neurological (acroparaesthesiae, altered temperature sensitivity) and gastrointestinal symptoms (altered bowel habits and abdominal pain), which were documented in about 80% and 60% of patients, respectively, at the time of evaluation and subsequent entry into FOS. Tinnitus, vertigo, fatigue and angiokeratoma were present in over 40% of patients. Symptoms were noted in early childhood and occurred with similar frequency in boys and girls, although the onset of symptoms was 2-5 y later in girls than in boys. There was an approximately 3-y delay from onset of symptoms to diagnosis, and patients were frequently misdiagnosed.Although the life-threatening complications of Fabry disease, such as stroke and renal and heart failure, are not seen in children, the present analysis shows that other symptoms are common and may have an impact on quality of life.