Objective:

This retrospective study examines three cases of symptomatic infantile Krabbe disease (IKD), highlighting the clinical relevance of electrodiagnostic (EDX) testing in diagnosis and management.

Background:

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. This case report features three patients, two of which were identified through newborn screening (NBS), while one was diagnosed prior to its implementation. All underwent EDX testing. The aim is to highlight the clinical importance of neurophysiological testing during the evaluation of Krabbe disease.

Design/Methods:

N/A

Results:

The sensory and motor nerve conduction studies of all three patients, as early as day 10 of life, revealed delayed and absent responses of the evoked potentials. The concentric needle electrode examination showed motor unit potentials with variably reduced recruitment. 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 all cases. Genetic testing identified pathogenic variants, including compound heterozygous deletions and mutations within the GALC gene. The two NBS-positive Krabbe patients underwent bone marrow transplantation.

Conclusions:

EDX testing is helpful in assessing NBS-positive Krabbe disease before confirmatory genetic testing results. In conjunction with genetic confirmation and GALC enzyme levels, EDX test results may be used to inform disease severity and counsel families. Currently, there are no uniform guidelines for the evaluation of patients with IKD detected on NBS. We suggest that EDX be included in the initial evaluation.