Abstract
We describe a case of 5,10-methenyltetrahydrofolate synthetase (MTHFS) deficiency characterized by microcephaly, global developmental delay, epilepsy, and cerebral hypomyelination. Whole exome sequencing (WES) demonstrated homozygosity for the R74X mutation in the MTHFS gene. The patient had the unexpected finding of elevated cerebrospinal fluid (CSF) neopterin. The novel finding of macrocytic anemia in this patient may provide a clue to the diagnosis of this rare neurometabolic disorder.
Highlights
Folate is involved in several aspects of cell division and homeostasis
methenyltetrahydrofolate synthetase (MTHFS) deficiency presents with cerebral hypomyelination in association with neurodevelopmental delay
The process by which cerebral folate deficiency disrupts myelination during development involves several mechanisms [5]. 5-MTHF deficiency leads to a downstream deficiency in S-adenosylmethionine (SAM), an important methyl donor
Summary
Folate is involved in several aspects of cell division and homeostasis. folate and its reduced metabolites act as coenzymes in nucleic acid synthesis, amino acid metabolism, methionine regeneration, neurotransmitter synthesis, and methylation [1]. MTHFS is one of the enzymes in the folate metabolism pathway and is encoded by the MTHFS gene located on chromosome 15q25.1. Rodan et al [4] described the first two cases of MTHFS deficiency due to heterozygous mutations in the MTHFS gene. Our case of MTHFS deficiency is the third ever reported and has novel findings of biallelic null mutations, macrocytic anemia, and elevated CSF neopterin.
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