Document Type

Article

Publication Date

9-10-2024

Identifier

DOI: 10.1016/j.gimo.2024.101891; PMCID: PMC11613563

Abstract

PURPOSE: This prospective, longitudinal study was designed to determine the natural history of Fabry disease (FD) in early pediatric patients across the disease spectrum.

METHODS: In this observational study of children under 5 years of age with variants in the GLA gene, prospective phenotypic and urinary biomarker data were collected annually over 5 years.

RESULTS: The study population included 40 participants (35 male, 5 female) with GLA variants including 15 with classic pathogenic variants (CFD), 6 with nonclassic pathogenic variants (NFD), and 19 with a variant of uncertain significance. The most common first symptoms reported were in participants with CFD and included gastrointestinal symptoms (13/15), heat intolerance (13/15), reduced sweating after previously sweating normally (6/15), and neuropathic pain/uncomfortable feet/hands (3/15). Mapping symptom onset and progression reveals a consistent pattern of frequency and severity occurring in the first years of life and beginning at an average age of 23.4 months (range 11-32 months) in males with CFD. Participants with nonclassic pathogenic variants and variant of uncertain significance did not exhibit consistency in symptom onset or progression during the study period.

CONCLUSION: This study highlights the onset and pattern of progression of the earliest Fabry-related symptoms in children with CFD.

Journal Title

Genet Med Open

Volume

2

First Page

101891

Last Page

101891

Keywords

Fabry disease; Lysosomal storage disorders; Natural history; Newborn screening; Pediatric

Comments

This article is available under the Creative Commons CC-BY-NC-ND license and permits non-commercial use of the work as published, without adaptation or alteration provided the work is fully attributed.

Publisher's Link: https://www.gimopen.org/article/S2949-7744(24)01037-9/fulltext

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