Late-onset Krabbe disease initially diagnosed as cerebroside sulfatase activator deficiency

Clinical and biochemical findings in a male subject with progressive encephalopathy and peripheral neuropathy are presented. Early development was normal. At age 3.5 years, he had seizures associated with fever. Subsequently, there was progressive neurologic deterioration. A CT brain scan at age 4 years, 2 months demonstrated multiple areas of variable density in the white matter. There was mild slowing of nerve conduction velocities and a sural nerve biopsy revealed segmental demyelinative neuropathy. Metachromatic leukodystrophy was suspected, but arylsulfatase A activity in leukocytes and fibroblasts was in the normal range. The cerebroside sulfate loading test on intact cultured fibroblasts showed attenuated hydrolysis leading to a tentative diagnosis of cerebroside sulfatase activator deficiency. However, the attenuated response of proband fibroblasts was not normalized by supplementation with activator in a reproducible manner, and urine showed hyperexcretion rather than deficiency of activator. Ultimately, an assay for galactosylceramide beta-galactosidase activity established a deficiency of this enzyme leading to the diagnosis of late-onset Krabbe disease.