Atypical Krabbe disease in two siblings harboring biallelic GALC mutations including a deep intronic variant

Krabbe disease (KD) is a rare lysosomal storage disorder caused by biallelic pathogenic variants in GALC. Most patients manifest the severe classic early-infantile form, while a small percentage of cases have later-onset types. We present two siblings with atypical clinical and neuroimaging phenotypes, compared to the classification of KD, who were found to carry biallelic loss-of-function GALC variants, including a recurrent 30 kb deletion and a previously unreported deep intronic variant that was identified by mRNA sequencing. This family represents a unique description in the KD literature and contributes to expanding the clinical and molecular spectra of this rare disorder.

Automated summary

We present two siblings with atypical clinical and neuroimaging phenotypes in Krabbe disease, who were found to carry biallelic loss-of-function GALC variants. This unique description expands the clinical and molecular spectra of this rare disorder.