A Case Report of Late Infantile Krabbe Disease: Expanding the Genotype-Phenotype Correlation and Autopsy Findings

Krabbe disease (KD) is an autosomal recessive neurodegenerative lysosomal disease typically caused by pathogenic variants in GALC, which encodes for the lysosomal galactosylceramidase enzyme. Age of onset is variable, with earlier symptom onset conferring a more severe, and ultimately fatal, disease course. We present a case of an 18-month-old previously healthy female diagnosed with late-infantile KD following a 3-month period of psychomotor regression and irritability. Clinical features included severe axial hypotonia with lower extremity spasticity and hyperreflexia. Whole genome sequencing disclosed a complex GALC genotype including two likely pathogenic variants, p.(Gly284Ser) and p.(Tyr314del), which had not been observed in compound heterozygosity prior. Magnetic resonance imaging displayed symmetric T2 hyperintensity of the central-parietal white matter. The patient ultimately died 6 months after diagnosis from rapidly progressing neurological deterioration. There was significant atrophy on neuropathologic examination, with diffuse globoid cell infiltrate at the supratentorial and infratentorial white matter with relative sparing of the frontal lobe on light microscopy. This patient’s novel genotype, imaging and pathologic findings expand our understanding of the phenotype-genotype correlation in individuals with KD.