A case of severe methylenetetrahydrofolate reductase deficiency presenting as neonatal encephalopathy, seizures, microcephaly and central hypoventilation

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