5,10‐methenyltetrahydrofolate synthetase deficiency: An extreme rare defect of folate metabolism in two Dutch siblings

Abstract Two siblings, presenting with a neurometabolic phenotype, were identified with 5, 10‐methenyltetrahydrofolate synthetase (MTHFS) deficiency. Whole genome sequencing in both patients demonstrated an homozygous MTHFS variant NM_006441.3( MTHFS ):c.434G > A, p.Arg145Gin, which has been described before. At baseline, both patients showed moderate hyperhomocysteinemia, decreased 5‐methyltetrahydrofolate (5MTHF), and increased 5‐formyltetrahydrofolate (5‐FTHF) in whole blood. In CSF, 5MTHF levels were in the low‐normal range and 5‐FTHF was strongly increased. In our novel enzyme assay, M... Mehr ...