Prospective characterization of early symptom onset and progression in young pediatric patients with variants in the gene across 5 years: Longitudinal data from the Fabry MOPPet Study.

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  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 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.