Selective Pyramidal Tract Involvement in Late-Onset Krabbe Disease

Abstract

A 10-y-old boy presented with gradually progressive leg stiffness and gait abnormality for 2 y. Subsequently, he had declining scholastic performance, hyperactivity, aggression with preserved vision and hearing. He was born to unrelated healthy parents. His premorbid development was normal. Examination revealed normocephaly (head circumference: 50 cm), asymmetric spasticity in lower limbs and pyramidal tract signs. Neuroimaging revealed asymmetric (right > left) T2-FLAIR hyperintensities in corona radiata, posterior limb of internal capsule and cerebral peduncles (corticospinal tracts) (Fig. 1). Isolated pyramidal tract involvement narrowed the etiological possibilities to late-onset Krabbe disease (LOKD), X-linked adrenoleukodystrophy (X-ALD) and other peroxismal disorders [1]. ß-galactocerebrosidase assay was low-normal (4.4 nmol/h/mg; range: 4–40 nmol/h/mg protein). Clinical exome sequencing revealed pathogenic compound heterozygous missense mutations inGALC gene (Exon 9; p.Gly323Arg and p.Tyr319Cys). LOKD usually presents with gait abnormality. Vision and hearing is often preserved if onset is after 5 y of age [2, 3]. There is parietooccipital deep white matter or selective pyramidal tract involvement [2]. Enzyme activity is often low but may be normal [4]. X-ALD is the closest radiological differential of LOKD in a boy. Clinical phenotype and absence of contrast enhancement are the distinguishing features. Globoid cells and enzyme assays are not sacrosanct [5]. Correlating radiology with genetics may be rewarding, even if clinical data is inconclusive.