Peripheral Neuropathy as an Early Marker in Newborn-Screened Krabbe Disease: The Value of Pre-Confirmatory Neurophysiological Testing.

INTRODUCTION: Krabbe disease, or globoid cell leukodystrophy, is a rare autosomal recessive neurodegenerative disorder characterized by deficient activity of the lysosomal enzyme galactosylceramidase (GALC). This deficiency leads to the toxic accumulation of psychosine, resulting in progressive demyelination and neuronal death. The clinical manifestations of Krabbe disease progress through different stages, starting with irritability, stiffness, and feeding difficulties, followed by myoclonic-like jerks in the upper and lower extremities, hypertonicity, and eventually severe hypotonia and lack of movement.

METHODS: This case report features two newborn screening patients with (NBS)-positive Krabbe disease who underwent electrodiagnostic (EDX) testing and hematopoietic stem cell transplantation (HSCT) soon after birth.

RESULTS: The EDX results indicated severe sensory-motor polyneuropathy of mixed demyelinating and axonal types. Biochemical analyses confirmed significantly reduced GALC enzyme activity and elevated psychosine levels in both cases. Genetic testing identified pathogenic variants, including compound heterozygous deletions and mutations within the GALC gene. At 6-month follow-up post-HSCT, one patient showed age-appropriate milestones and improvement in motor amplitudes on repeat nerve conduction studies.

DISCUSSION: EDX testing is helpful in assessing NBS-positive Krabbe disease before confirmatory testing results become available. In conjunction with genetic confirmation and GALC enzyme levels, EDX test results were useful to counsel families that their seemingly normal newborn has severe disease and facilitated discussion toward timely treatment with HSCT. We suggest that EDX be included in the initial and follow-up evaluation of patients with Krabbe disease undergoing HSCT.