Diagnostic Value of the MAT1A Gene Mutations in Methionine Adenosyltransferase I/III Deficiency: Possible Relevance to Various Neurological Manifestations

Methionine adenosyltransferase I/III (MAT I/III) deficiency is a metabolic disorder exhibiting persistent hypermethioninemia and neurological problems such as mental retardation and movement disorders by brain demyelination. Current diagnosis of MAT I/III deficiency completely depends upon newborn mass screening. Recently, correlation between the type of mutation of the MAT1A gene and clinical presentation has been investigated. The most common mutation, heterozygous for the autosomal dominant Arg264His mutation, is a relatively benign phenotype which requires no treatment. In contrast, care must be taken on the Arg292Cis mutation, especially if compounded with mutations at Arg356 (Arg356Pro, Arg356Leu, and Arg356Gln), for association of myelination disorder. Since MAT I/III catalyzes conversion of methionine to produce S-adenosylmethionine (SAM), supplementation of SAM is a therapeutic strategy to improve neurological problems. Hypermethioninemia can be corrected by methionine restriction; however, it may cause depletion of SAM. DNA testing is important for early diagnosis to prevent neurological manifestations.