A case of Krabbe disease presenting with hydrocephalus

Abstract

Krabbe disease, or globoid cell leukodystrophy, is a rare autosomal recessive lysosomal storage disorder caused by deficiency of galactocerebrosidase (GALC) enzyme activity. While classic infantile presentation typically includes irritability, spasticity, and developmental regression, this report describes an atypical initial manifestation with acute hydrocephalus. A four-month-old female infant, born to consanguineous parents, presented with poor feeding, lethargy, hypotonia, and episodic staring. Physical examination revealed failure to thrive with normal head circumference. Neuroimaging demonstrated acute hydrocephalus and characteristic white matter abnormalities including T2 hyperintensities in the dentate nucleus and internal capsule. Cerebrospinal fluid (CSF) analysis showed significantly elevated protein levels. The diagnosis was confirmed through markedly reduced galactocerebrosidase activity (0.2 nmol/hour/mg protein; reference >0.3) and identification of a homozygous pathogenic variant in the GALC gene (c.908C>T p.Ser303Phe). This case emphasizes that acute hydrocephalus can represent an uncommon but critical presenting feature of infantile Krabbe disease. In infants with unexplained neurological deterioration and hydrocephalus, particularly with consanguineous family history, prompt metabolic evaluation including cerebrospinal fluid analysis and specific enzyme assays is essential for diagnosis. Early identification remains crucial for considering potential therapeutic interventions, including hematopoietic stem cell transplantation.