Hypomyelination and reversible white matter attenuation in 3-phosphoglycerate dehydrogenase deficiency

White matter abnormalities are a feature of many inborn errors of metabolis m and magnetic resonance imaging (MRI) of the brain has become an important tool in the diagnostic workup of these disorders. Recently, patients were reported with a potentially treatable disorder of serine biosynthesis. They presented with congenital microcephaly, severe psychomotor retardation and intractable seizures. Low concentrations of the amino acids serine, glycin e as well as 5-methyltetrahydrofolate were found in plasma and CSF and were due to a deficiency of the enzyme 3-phosphoglycerate dehydrogenase (3-PGDH ). We studied four patients aged 10 months to 7 years by MRI before and aft er treatment with amino acids with a follow-up of 16 months to 6 years. Mag netic resonance spectroscopy (MRS) was performed in two patients at 4 and 1 6 months of treatment. Pre-treatment MRI demonstrated hypomyelination and p rofound white matter attenuation in all patients. During treatment, a signi ficant increase in white matter volume was found and a progress of myelinat ion in two patients. The most striking finding on MRS during treatment was an elevated level of white matter choline. Serine biosynthesis defects have to be considered in the differential diagnosis of patients with mental ret ardation, microcephaly, seizures, and on MRI hypomyelination and white matt er attenuation.