title: 5,10-Methylenetetrahydrofolate reductase deficiency with progressive polyneuropathy in an infant.
abstract: 5,10-Methylenetetrahydrofolate reductase (MTHFR) deficiency is the most prevalent inborn error of folate metabolism, and has variable clinical manifestations from asymptomatic to severe psychomotor retardation, microcephalus and seizure. In untreated infantile cases, it predominantly affects the central nervous system, which is sometimes fatal. On the other hand, peripheral nerve involvement is uncommon. We present a severe infantile case of MTHFR deficiency that manifested unilateral phrenic nerve palsy with communicating hydrocephalus, developmental delay and died at 11months of age. An enzymatic study confirmed MTHFR deficiency with residual activity of 0.75% of mean control values in cultured fibroblasts. Mutation analysis of the MTHFR gene revealed homozygous, tandem missense mutations c.[446G>T; 447C>T] in exon 3 of the MTHFR gene converting glycine to valine (Gly149Val). In MTHFR deficiency, betaine may improve the symptoms if started immediately after birth by reducing the level of serum homocysteine and increasing that of methionine. Our results show that we should be aware of possible inborn errors of folate metabolism such as MTHFR deficiency, in infants with unexplained developmental delay manifesting rapidly progressive polyneuropathy.
authors.affiliation: Division of Neurology, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Tsuji
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takagi
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Sameshima
authors.forename: Mizue
authors.initials: M
authors.lastname: Iai
authors.forename: Sumimasa
authors.initials: S
authors.lastname: Yamashita
authors.forename: Hiroko
authors.initials: H
authors.lastname: Shinbo
authors.forename: Noritaka
authors.initials: N
authors.lastname: Furuya
authors.forename: Kenji
authors.initials: K
authors.lastname: Kurosawa
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Osaka
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D044466:Asian People; D001921:Brain / Q000473:pathology; D006712:Homocystinuria / Q000150:complications* / Q000235:genetics*; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000172:deficiency / Q000235:genetics; D008969:Molecular Sequence Data; D009128:Muscle Spasticity / Q000150:complications* / Q000235:genetics*; D020125:Mutation, Missense; D011115:Polyneuropathies / Q000209:etiology* / Q000235:genetics*; D011618:Psychotic Disorders / Q000150:complications / Q000235:genetics; D016415:Sequence Alignment; D013763:Tetrahydrofolates / Q000378:metabolism*
chemical_list: D013763:Tetrahydrofolates; C013123:5,10-methylenetetrahydrofolic acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2)