Pedigree Case Report of adult-onset phenotypically heterogeneous Krabbe disease
TL;DR
This report describes a family in which identical homozygous GALC mutations presented with markedly distinct clinical phenotypes and disease trajectories during adulthood, thereby substantially expanding the current understanding of the phenotypic spectrum of Krabbe disease and offering novel insights into the differential diagnosis of adult-onset neurodegenerative disorders.
Abstract
Background Krabbe disease is a rare autosomal recessive leukodystrophy, typically considered a fatal disorder of infancy. Adult-onset forms are uncommon and diagnostically challenging due to their nonspecific presentations. Case presentation We report a consanguineous Han Chinese pedigree comprising two siblings diagnosed with adult-onset Krabbe disease, both carrying the identical homozygous GALC c.1048T>G (p.Phe350Val) mutation. Notably, the age at onset differed by 26 years between the two siblings (49 years vs. 23 years), with markedly distinct clinical trajectories—one presenting with progressive dysarthria and peripheral neuropathy, and the other with spastic paraplegia, ultimately leading to wheelchair dependence. Conclusion This report describes a family in which identical homozygous GALC mutations presented with markedly distinct clinical phenotypes and disease trajectories during adulthood, thereby substantially expanding the current understanding of the phenotypic spectrum of Krabbe disease and offering novel insights into the differential diagnosis of adult-onset neurodegenerative disorders.