Intractable Rare Dis Res. 2026;15(1):106-114. (DOI: 10.5582/irdr.2025.01070)

Multidisciplinary approach to the assessment and management of children with Fabry disease: Insights from the Chinese Children Genetic Kidney Disease Database

Wang J, Liu J, Chen J, Zhang A, Mao J, Shen T, Jiang X, Wang M, Tao Y, Zhao B, Wang X, Li Z, Chen A, Chen C, Zhang B, Zhang D, Zhao L, Zhao Y, Bao Y, Bai L, Liu C, Wang F, Hu F, Chen M, Lv X, Sun S, Shen Q, Xu H

Fabry disease (FD) is a rare multisystemic lysosomal storage disorder with diverse pediatric manifestations. This multicenter study analyzed 64 children with FD from the Chinese Children Genetic Kidney Disease Database following establishment of the first national pediatric FD multidisciplinary team (MDT) in April 2020, which expanded to 15 centers by January 2022. Median diagnostic age was 11.4 years in males and 9.4 years in females, with diagnostic delays of 4.4 and 4.0 years, respectively. Family screening accounted for most female diagnoses (72.2%), while 6.5% of males were incidentally detected during genetic testing for other diseases. Missense variants predominated (65.2% males, 66.7% females). Biochemically, males had markedly reduced α-Gal A activity (0.6 ± 0.4 μmol/L/h), and most patients showed elevated globotriaosylsphingosine (Lyso-GL-3), including 87.0% of males and 83.3% of females. Neuropathic pain was the most common initial symptom (52.2% males, 27.8% females; median onset 8 years), primarily acroparesthesia (92.1% and 85.7%, respectively). Other frequent features included anhidrosis/hypohidrosis (58.7% males, 11.1% females). Multisystem involvement included cardiac (arrhythmia n = 11, left ventricular hypertrophy n = 3), pulmonary (obstructive airway disease in 24.2% of males), skeletal (low bone mineral density in 4/7 tested males), and renal manifestations (reduced glomerular filtration rate (GFR) in 3). Thirtyseven patients received enzyme replacement therapy at median ages of 12.9 years (males) and 11.7 years (females). This first nationwide pediatric FD cohort highlights substantial diagnostic delays and underscores the importance of MDT collaboration, family screening, and early recognition to improve outcomes in affected children.

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