The beneficial effects of oral L-serine (up to 500 mg/kg/day) and glycine (200 mg/kg/day) in 2 siblings, aged 7 and 5 years, with 3-phosphoglycerate dehydrogenase (3-PGDH) deficiency are reported from University Children’s Hospital, Utrecht, The Netherlands. The patients were born with microcephaly, development was retarded, and seizures started at 1 year, 10 to 50 daily, and were refractory to sodium valproate and clonazepam. EEG’s showed multifocal epileptiform discharges. MRI showed cortical atrophy and hypomyelination. Laboratory tests showed megaloblastic anemia, thrombocytopenia, low plasma concentrations of serine and glycine, and low CSF methyltetrahydrofolate concentration. 3-PGDH activity in cultured skin fibroblasts was deficient (3.9 and 1.7 mU/mg protein). The parents 3-PGDH activity was normal (23 and 27 mU/mg of protein). Amino acid treatment resulted in complete control of seizures in 2 weeks, and the EEG abnormalities resolved in 6 months. Plasma serine and glycine concentrations also became normal during therapy, and no adverse effects were noted during 12 months of follow-up. [1]

COMMENT. 3-Phosphoglycerate dehydrogenase (3-PGDH) deficiency is a rare inborn error of serine biosynthesis recently recognized and manifested by congenital microcephaly, seizures, and psychomotor retardation. Low concentrations of serine and glycine are found in plasma and CSF during fasting. Whereas serine supplements alone correct the anemia and are partially effective against seizures, the addition of glycine results in complete seizure control and improves behavior and alertness. Serine metabolism should be checked by fasting plasma amino acid determinations in infants with microcephaly and seizures.