3-Phosphoglycerate dehydrogenase deficiency
Incidence
Autosomal recessive. Less than 10 cases reported.
Clinical Characteristics
3-phosphoglycerate dehydrogenase deficiency is a severe but treatable disorder of serine synthesis, first described in 1996. 3 Phosphoglycerate dehydrogenase (3PGDH) deficiency is a rare disorder of serine and glycine biosynthesis characterized by severe psychomotor retardation and seizures. The main clinical characteristics are: Microcephaly, megaloblastic anemia, thrombocytopenia, seizures, spastic tetraplegia, nystagmus, cataract, hypogonadism. This disorder is potentially treatable as the convulsions and biochemical abnormalities can be effectively ameliorated by amino acid supplementation therapy. Serine concentrations were markedly decreased in the cerebrospinal fluid of two brothers with congenital microcephaly, profound psychomotor retardation, hypertonia, epilepsy, growth retardation, and hypogonadism. The youngest boy also had congenital bilateral cataract. Magnetic resonance imaging of the brain showed evidence of dysmyelination. Plasma serine as well as plasma and cerebrospinal fluid glycine concentrations were also decreased but to a lesser extent. Treatment with oral serine in the youngest patient significantly increased cerebrospinal fluid serine and abolished the convulsions. In fibroblasts of both patients, a decreased activity was demonstrated of 3-phosphoglycerate dehydrogenase, the first step of serine biosynthesis (22% and 13% of the mean control value). Four patients were studied 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.This is an unusual disorder as the great majority of aminoacidopathies are catabolic defects. There is parental consanguinity. Cerebrospinal fluid serine concentrations is increased by oral serine. It is a severe but potentially treatable inborn error of metabolism.
Precipitants
no
Provocation Tests
no
Diagnostic Procedures
EB-F. 3-phosphoglycerate dehydrogenase deficiency in fibroblasts. Decreased serine anc glycine cerebrospinal fluid concentration. Biochemical abnormalities in this disorder are found in the fasted state and consist of low concentrations of the amino acids serine and glycine in plasma and cerebrospinal fluid. LOW: 5-methyl-THF (CSF), serine (CSF), glycine (CSF).
Brain \'dysmyelination\' on NMR.