Hypomyelination and reversible white matter attenuation in 3-phosphoglycerate dehydrogenase deficiency.
White matter abnormalities are a feature of many inborn errors of metabolism and magnetic resonance imaging (MRI) of the brain has become an important tool in the diagnostic work-up 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, glycine 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 after treatment with amino acids with a follow-up of 16 months to 6 years. Magnetic resonance spectroscopy (MRS) was performed in two patients at 4 and 16 months of treatment. Pre-treatment MRI demonstrated hypomyelination and profound white matter attenuation in all patients. During treatment, a significant increase in white matter volume was found and a progress of myelination 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 retardation, microcephaly, seizures, and on MRI hypomyelination and white matter attenuation.
de Koning
T J
TJ
Department of Pediatric Metabolic Diseases, University Medical Centre Utrecht, The Netherlands. t.dekoning@wkz.azu.nl
Jaeken
J
J
Pineda
M
M
Van Maldergem
L
L
Poll-The
B T
BT
van der Knaap
M S
MS
D000596:Amino Acids / Q000627:therapeutic use; D002237:Carbohydrate Dehydrogenases / Q000172:deficiency*; D002540:Cerebral Cortex / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D002794:Choline / Q000096:biosynthesis; D003711:Demyelinating Diseases / Q000209:etiology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000209:etiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008831:Microcephaly / Q000209:etiology*; D050543:Phosphoglycerate Dehydrogenase; D012640:Seizures / Q000209:etiology*; D012694:Serine / Q000096:biosynthesis
D000596:Amino Acids; D012694:Serine; D002237:Carbohydrate Dehydrogenases; D050543:Phosphoglycerate Dehydrogenase; D002794:Choline