Spectrum of mutations associated with methionine adenosyltransferase I/III deficiency among individuals identified during newborn screening in Japan.

Abstract

Methionine adenosyltransferase I/III deficiency (MAT I/III deficiency) is an inborn error of metabolism that results in isolated persistent hypermethioninemia. Definitive diagnosis is now possible by molecular analyses of the MAT1A gene. Based on newborn screening (NBS) data collected between 2001 and 2012 in Hokkaido, Japan, the estimated incidence of MAT I/III deficiency was 1 in 107,850. 24 patients (13 males, 11 females) from 11 prefectures in Japan were referred to our laboratory for genetic diagnosis of MAT I/III deficiency. They were all found between 1992 and 2012 by the NBS program in each region. In these 24 individuals, we identified 12 distinct mutations; 14 patients were heterozygous for an R264H mutation; R264H caused an autosomal dominant and clinically benign phenotype in each case. The mutations in the other 10 patients showed autosomal recessive inheritance and included eight novel MAT1A mutations. Putative amino acid substitutions at R356 were observed with six alleles (three R356P, two R356Q, and one R356L). MAT I/III deficiency is not always benign because three of our cases involved brain demyelination or neurological complications. DNA testing early in life is recommended to prevent potential detrimental neurological manifestations.

• Authors: Masayoshi Nagao, Toju Tanaka, Mahoko Furujo
• Journal: Molecular genetics and metabolism (Mol Genet Metab) Vol. 110 Issue 4 Pg. 460-4 (Dec 2013) ISSN: 1096-7206 [Electronic] United States
• PMID: 24231718 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Methionine
• Glycine N-Methyltransferase
• MAT1A protein, human
• Methionine Adenosyltransferase

Topics

• Alleles
• Amino Acid Metabolism, Inborn Errors (diagnosis, genetics)
• Brain
• Female
• Glycine N-Methyltransferase (deficiency)
• Humans
• Infant, Newborn
• Japan
• Male
• Methionine (genetics, metabolism)
• Methionine Adenosyltransferase (deficiency, genetics)
• Mutation
• Neonatal Screening
• Nervous System Diseases (etiology, genetics)
• Phenotype