SHMT2, the mitochondrial form of serine hydroxymethyltransferase, is a pivotal enzyme located at the intersection of the amino acid and folic acid metabolic pathways. SHMT2 performs the first step in a series of reactions that provide one-carbon units covalently bound to folate species in mitochondria: it transfers one-carbon units from serine to tetrahydrofolate (THF), generating glycine and 5,10-methylene-THF. The mitochondrial dysfunction in proliferating cells probably contributes to microcephaly and polymicrogyria.
Quadriceps and myocardial biopsies show myopathic changes and the presence of “ragged red” fibers, suggestive of defective mitochondria.
SHMT2