5,10-Methylenetetrahydrofolate reductase deficiency with progressive polyneuropathy in an infant.
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.
Tsuji
Megumi
M
Division of Neurology, Kanagawa Children's Medical Center, Yokohama, Japan.
Takagi
Atsushi
A
Sameshima
Kiyoko
K
Iai
Mizue
M
Yamashita
Sumimasa
S
Shinbo
Hiroko
H
Furuya
Noritaka
N
Kurosawa
Kenji
K
Osaka
Hitoshi
H
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*
D013763:Tetrahydrofolates; C013123:5,10-methylenetetrahydrofolic acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2)