A case of severe methylenetetrahydrofolate reductase deficiency
presenting as neonatal encephalopathy, seizures, microcephaly and central hypoventilation
Affiliations: Department of Genetics, Pediatric Institute, Kuala
Lumpur Hospital, Kuala Lumpur, Malaysia | Department of Clinical Chemistry, VU University
Medical Center, Amsterdam, The Netherlands
Note: [] Correspondence: Dr. Shanti Balasubramaniam, Department of
Genetics, Pediatric Institute, Kuala Lumpur Hospital, 50586 Jalan Pahang, Kuala
Lumpur, Malaysia. Tel.: +61 40 430 2585; Fax: +61 60 6764 7092; E-mail: [email protected]
Abstract: Methylenetetrahydrofolate reductase (MTHFR) is a key regulatory
enzyme in the remethylation of homocysteine to methionine.
S-adenosylmethionine, formed from methionine and adenosine triphosphate, is the
methyl donor in crucial reactions for brain development and function. MTHFR
deficiency is the most prevalent inborn error of folate metabolism and is
characterized by hyperhomocysteinemia and hypomethioninemia. A broad clinical
spectrum includes psychomotor retardation, microcephaly, seizures, central
respiratory failure and death. Premature atherosclerosis, arterial and venous
thrombosis or psychiatric manifestations occur in the late onset forms. We
report a female neonate with severe MTHFR deficiency presenting with neonatal
encephalopathy, congenital microcephaly, seizures, central hypoventilation with
gross cerebral atrophy, hypomyelination and pontine hypoplasia on magnetic
resonance imaging of brain. She succumbed at 10 wk of age despite treatment
with oral S-adenosylmethionine, betaine, folinic acid, riboflavin and
hydroxycobalamin.
Keywords: MTHFR deficiency, remethylation of homocysteine, severe neurological impairment, microcephaly, seizures, central hypoventilation
