title: Novel c.2216T > C (p.I739T) mutation in exon 13 and c.1481T > A (p.L494X) mutation in exon 8 of MUT gene in a female with methylmalonic acidemia.
abstract: We report herein a 1.5-year-old girl with methylmalonic acidemia (MMA) in whom two missense mutations were found: a novel I739T mutation located in exon 13 and the L494X mutation in exon 8. The results of organic acid test showed a pronounced increase in methylmalonate excretion with increased methylcitrate and 3-OH-propionate excretion, leading to a diagnosis of MMA, and Vitamin B12 administration was started. Analysis of the mut gene confirmed a T-to-A substitution at nucleotide position 1481 in exon 8 and a T-to-C substitution at nucleotide position 2216 in exon 13, leading to the amino acid isoleucine at position 739 being changed to threonine, resulting in c.2216T > C (p.I739T). The patient has now been on high-dose oral administration of Vitamin B12 and carnitine therapy (900 mg of levocarnitine chloride) for 5 years without experiencing further attacks, and her cognitive and motor development is normal. Further tests on residual enzyme activity, as well as experience with more cases, may shed light on the relationship between gene mutations and phenotypes in MMA.
authors.affiliation: Department of Pediatrics, School of Medicine, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Shimotsuga, Tochigi, 321-0293, Japan. geo@dokkyomed.ac.jp
authors.forename: George
authors.initials: G
authors.lastname: Imataka
authors.forename: Osamu
authors.initials: O
authors.lastname: Sakamoto
authors.forename: Hideo
authors.initials: H
authors.lastname: Yamanouchi
authors.forename: Shigemi
authors.initials: S
authors.lastname: Yoshihara
authors.forename: Yuki
authors.initials: Y
authors.lastname: Omura-Hasegawa
authors.forename: Go
authors.initials: G
authors.lastname: Tajima
authors.forename: Osamu
authors.initials: O
authors.lastname: Arisaka
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000188:drug therapy / Q000235:genetics*; D001483:Base Sequence; D002331:Carnitine / Q000627:therapeutic use; D002951:Citrates / Q000378:metabolism; D005091:Exons; D005260:Female; D006801:Humans; D007223:Infant; D008764:Methylmalonic Acid / Q000378:metabolism; D008765:Methylmalonyl-CoA Mutase / Q000235:genetics*; D020125:Mutation, Missense; D011422:Propionates / Q000378:metabolism; D014805:Vitamin B 12 / Q000627:therapeutic use; D014803:Vitamin B Complex / Q000627:therapeutic use
chemical_list: D002951:Citrates; D011422:Propionates; D014803:Vitamin B Complex; C031605:2-methylcitric acid; D008764:Methylmalonic Acid; D008765:Methylmalonyl-CoA Mutase; D014805:Vitamin B 12; D002331:Carnitine