Long-term neurological outcome after hematopoietic stem cell transplant in juvenile Krabbe disease

Globoid cell leukodystrophy (GLD) is a progressive neurodegenerative disease caused by galactocerebrosidase deficiency. Juvenile phenotypes-onset between ages 3 and 16-account for up to 25% of cases. Hematopoietic stem cell transplantation (HSCT) is the only available treatment, yet only eight juvenile-onset cases treated with HSCT have been reported, with heterogeneously collected data. We aim to comprehensively evaluate long-term neurological outcomes post-HSCT in juvenile GLD.

We conducted a retrospective study of all juvenile GLD patients treated with HSCT and followed at our Institution. We assessed survival, neurological status, disability (modified Rankin Scale), cognitive outcomes, GALC activity, serial MRIs (Loes score), evoked potentials (internal scoring system), and nerve conduction studies at pre-HSCT, first post-HSCT visit, and last follow-up.

Six biochemically and genetically confirmed juvenile GLD cases were included. Four were symptomatic at diagnosis; two were pre-symptomatic. All survived to last follow-up (range 9 years, 2 months-19 years, and 8 months). Four achieved near-normal cognitive, motor, and functional status. Two symptomatic patients-with extensive pre-HSCT white matter disease and specific pre-HSCT clinical features (epilepsy and cognitive impairment)-had suboptimal outcomes. Loes scores stabilized/improved in four patients; GALC enzyme activity normalized in all. Electrophysiological measures mostly remained stable.

HSCT significantly impacts the natural history of juvenile GLD, resulting in largely optimal long-term outcomes, preserved quality of life, and minimal disability. Standardized pre-transplant assessments are critical. High pre-HSCT Loes scores, epilepsy, and cognitive impairment could be prognostic indicators, highlighting the importance of early intervention based on comprehensive instrumental evaluations.