BIOCHEMICAL PATHOGENESIS OF SUBACUTE COMBINED DEGENERATION OF THE SPINAL-CORD AND BRAIN

In humans, subacute combined degeneration of the spinal cord and brain , a primary demyelinating disease, is caused by cobalamin or methyltet rahydrofolate deficiency. Experimental studies into its pathogenesis s uggest that dysfunction of the methyl-transfer pathway may be the caus e. Compelling evidence for this comes from the study of inborn errors of cobalamin metabolism where deficiency of methylcobalamin, but not d eoxyadenosylcobalamin, is associated with demyelination. Recent studie s have focused upon inborn errors of the methyl-transfer pathway. Cere brospinal fluid concentrations of metabolites of the methyl-transfer p athway have been measured in humans with sequential errors of the path way and correlated with demyelination demonstrated on magnetic resonan ce imaging of the brain. This has provided new data suggesting that de ficiency of S-adenosylmethionine is critical to the development of dem yelination in cobalamin deficiency.