Adult-onset Krabbe disease manifesting as Charcot- Marie-Tooth disease

Abstract

Krabbe disease (KD) is a progressive lysosomal storage disorder characterized by the deficiency of β-galactocerebrosidase (GALC). It mainly manifests as central nervous system involvement, but peripheral nervous system damage is also found. Although it can appear as a widespread neuropathy, it is very rare to manifest in a form similar to Charcot-Marie-Tooth disease (CMT). A 34-year-old woman presented with progressive gait disturbance and foot deformity. There were no other medical or family history of abnormalities. Nerve conduction studies showed demyelinating neuropathy, and brain MRI showed white matter hyperintensities. Sequencing of PMP22 gene was normal, followed by next-generation sequencing (NGS). Potential compound heterozygous variants in the GALC gene were found; additionally a decrease in GALC enzymatic activity was confirmed, and KD was diagnosed. Although CMT has been previously diagnosed through a single genetic test, since the introduction of NGS, various genetic mutations have been identified in patients suspected of having CMT. In addition to the phenotypes mainly found in KD, other unusual phenotypes have also been found. In this case, we identified a unique clinical phenotype similar to CMT in a KD patient. We also confirmed the clinical usefulness of NGS by demonstrating in a KD patient diagnosed through NGS, who was not identified by conventional genetic mutation testing.