A slowly progressive cerebellar syndrome associated with disturbed folate transfer across the choroid plexus is reported in an 18-year-old male who presented with incoordination of hands and feet at the Institute of Neurology, University Hospital of Nijmegen, The Netherlands. A rapidly progressive bilateral sensorineural hearing loss had preceeded the onset of ataxia which was complicated by dysarthria and dysphagia, and was followed at 21 years, with muscle cramps and at 26 years, with a distal spinal muscular atrophy and pyramidal tract signs of hyperreflexia and Babinski reflexes. Cranial CT showed cerebral and cerebellar atrophy and hypodensities in the basal ganglia. The serum (9.6-10.5 nmol/1) and red cell (371) folate levels were normal while the CSF folate was severely depleted (1.4-2.6 nmol/1; ref normal range 14-42). Analyses of folate binding protein in CSF performed at laboratories in Denmark showed abnormalities that indicate a defective folate transport into the CNS. [1]

COMMENT. Folate occurs in higher concentrations in CSF than in plasma, and it enters the CSF against a concentration gradient. Folate binding proteins in the plasma membrane of the choroid plexus are essential in the transport of folate to the CSF and CNS. Low CSF folate has been reported in inborn errors of metabolism, Kearns-Sayre syndrome, and HIV infection. Neurologic manifestations of inherited disorders of folate metabolism include mental and motor retardation, ataxia, and seizures. Consanguinity of the parents of the above patient suggests an autosomal recessive inheritance.

In addition to folate and vitamin E deficiencies, other degenerative ataxias resembling Friedreich’s ataxia that may be amenable to dietary supplements or modifications include vitamin B12 and biotin deficiencies and Refsum’s disease, responsive to a diet low in phytol and phytanic acid. (Progress in Pediatric Neurology, Chicago, PNB Publ, 1991, p 480).