057 A rare presentation of a rare disease: adult onset krabbe’s disease presenting with progressive hypertrophic polyradiculoneuropathy

Introduction Globoid Cell Leukodystrophy (Krabbe’s disease) is a rare autosomal recessive condition caused by defects in the lysosomal enzyme galactosylceramidase. The disease typically occurs in infants and is rapidly progressive. Fewer than 5% of cases develop symptoms in adulthood, the majority of which present with spastic paraparesis. Case A 40-year-old Italian man presented with a 20 year history of gradually progressive asymmetrical hand paraesthesias and weakness. EMG demonstrated demyelinating features and absent sensory responses. CSF examination revealed elevated protein with no cells and negative oligoclonal bands. Treatment with intravenous immunoglobulin (IVIg) was commenced and continued for 2 years for presumed CIDP without clinical response. Upper limb wasting and weakness progressed over the following 10 years with associated loss of reflexes, prompting consideration of an underlying genetic neuropathy. DNA testing for common CMT mutations was negative. MRI cervical spine and brachial plexus demonstrated diffuse bilateral non-enhancing enlargement of cervical nerve roots. IVIg was recommenced over the next 10 years with continued clinical deterioration to the point of bilateral flail arms with relatively preserved lower limb motor function, in addition to bulbar and respiratory dysfunction by age 64. MRI brain demonstrated thickening of a number of cranial nerves without contrast enhancement, and extensive T2-hyperintensity of periventricular white matter. Next generation sequencing revealed two novel mutations in the galactosylceramidase (GALC) gene, and beta-galactocerebrosidase activity was reduced, confirming the diagnosis of Krabbe’s disease. Conclusion This case highlights an unusual presentation of Krabbe’s disease with progressive hypertrophic polyradiculoneuropathy, associated with a novel genetic mutation.