Molecular genetics of hepatic methionine adenosyltransferase deficiency

Hepatic methionine adenosyltransferase (MAT) deficiency is caused by mutati ons in the human MA nil gene that abolish or reduce hepatic MAT activity th at catalyzes the synthesis of S-adenosylmethionine from methionine and ATP. This genetic disorder is characterized by isolated persistent hypermethion inemia in the absence of cystathionine P-synthase deficiency, tyrosinemia, or liver disease. Depending on the nature of the genetic defect, hepatic MA T deficiency can be transmitted either as an autosomal recessive or dominan t trait. Genetic analyses have revealed that mutations identified in the MA TIA gene only partially inactivate enzymatic activity, which is consistent with the fact that most hepatic MAT-deficient individuals are clinically we ll. Two hypermethioninemic individuals with null MA TIA mutations have deve loped neurological problems, including brain demyelination, although this c orrelation is by no means absolute. Presently, it is recommended that a DNA -based diagnosis should be performed for isolated hypermethioninemic indivi duals with unusually high plasma methionine levels to assess if therapy aim ed at the prevention of neurological manifestations is warranted. Published 1999 by Elsevier Science Inc. All rights reserved.