Background Methylene tetrahydrofolate reductase (MTHFR) deficiency is a rare autosomal recessive disorder, caused by mutated alleles of the MTHFR gene. Since this enzyme catalyzes the conversion of 5.10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, its deficiency results in hyperhomocysteinemia, homocystinuria and hypomethionemia. The clinical manifestations vary from asymptomatic to fatal disease with severe neurodevelopmental delay and epileptic encephalopathy.

Case Our patient was a two-month old female born from consanguineous parents presenting with infantile spasms, hypotonia and microcephalus. She was transferred to our pediatric intensive care unit for respiratory failure. The biochemical work-up revealed low vitamin B12 level: 152.6 pg/ml (197–866 pg/ml), close to lower limit of folate: 4.62 ng/ml (3.1–17.5 ng/ml), increased homocysteine level: 9.85 nmol/ml (0–1 nmol/ml), and very low methionine level: 7.32 nmol/ml (19–51 nmol/ml). Magnetic resonance imaging of the brain showed white matter changes of the frontal lobes, posterior legs of capsula interna, pons and nucleus dentatus consistent with demyelination. MTHFR deficiency was suspected, and treatment with folinic acid, vitamin B12, methionine and betaine was initiated. The peripheral blood DNA analysis of the patient demonstrated a homozygous mutation of c.1015T>G in MTFHR gene. Both parents were confirmed to be asymptomatic heterozygote carriers. Despite treatment, the prognosis was fatal.

Conclusions As related reports suggest better prognosis with early treatment, pediatricians need to consider MTHFR deficiency in similar cases. Prenatal diagnosis is available and should be encouraged for the future pregnancies.