An unusual case of late-infantile onset Krabbe disease with selective bilateral corticospinal tract involvement, peripheral demyelinating neuropathy, and mild phenotype

Excerpt

A 17-year-old boy was evaluated for a history of mild delay in motor milestones by the 8 months of age and frequent falls from his first step by the age of 18 months. During the following of 13 years, the course has been stable and he never experienced motor or cognitive regression, seizures, or visual problems. Neurological examination showed no cognitive deficits, no difficulties with speech, and normal visual acuity and fields. Muscle hypotrophy of lower limbs was evident (Fig. 1a). He could stand and walk unsupported with mild stepping gait. Bright osteo-tendinous reflexes of the four limbs were present, without increased tone, Babinski sign, or clonus. No strength deficits were present, except for a mild weakness of bilateral extensor hallucis longus (MRC 4/5). Romberg and cerebellar tests, sensory, and vibration sense were normal. Nerve conduction studies revealed sensory-motor demyelinating neuropathy of the lower limbs. Motor-evoked potentials showed increased central conduction time. Brain MRI revealed white-matter lesions with selective corticospinal tract involvement (Fig. 1b–i). Metabolic analysis (i.e., plasma acylcarnitine, amino acid, and very-long-chain fatty acids profiles; isoelectrofocusing of serum transferrin; urinary organic acid profile) were unrevealing. Leukocyte lysosomal galactocerebrosidase activity was markedly reduced (1 nmol/mg; normal range 9–70). Sanger sequencing of GALC reveled compound heterozygous c.1151T > C (p.I384T) and c.302A > G (p.E101G) mutations. The c.302A > G is a novel mutation, predicted to be pathogenic by in silico prediction tools (i.e., PolyPhen-2 and Mutation Taster). Segregation analysis revealed a maternal inheritance of the c.1151T > C change and a paternal inheritance of the c.302A > G change. …