Methionine adenosyltransferase I/III deficiency: neurological manifestations and relevance of S-adenosylmethionine.

Methionine adenosyltransferase I/III (MAT I/III) deficiency, caused by mutations in the MAT1A gene, is an inherited metabolic disorder characterized by persistent hypermethioninemia, usually detected by newborn mass screening. There is a wide range of clinical manifestations, from completely asymptomatic to neurological problems associated with brain demyelination. Physiological role of S-adenosylmethionine (SAM), the metabolic product of methionine catalyzed by MAT, in the central nervous system has been investigated in vivo and in vitro, and case reports demonstrated an effectiveness of supplementary treatment of SAM in the improvement of neurological development and myelination. Methionine restriction can be an additional therapeutic strategy because hypermethioninemia alone may be neurotoxic; however, lowering methionine carries a risk to decrease the synthesis of SAM.