3-Phosphoglycerate Dehydrogenase Deficiency (PHGDH)

3-Phosphoglycerate dehydrogenase deficiency is an autosomal recessive disorder caused by pathogenic variants in the PHGDH gene. It has been reported in patients of different ethnicities, although it has an increased prevalence in individuals of Ashkenazi Jewish descent. Onset is in infancy or early childhood, and clinical features include a small head size (microcephaly), severe psychomotor retardation, and seizures. Progressive loss of brain cells leads to brain atrophy and hypomyelination. Although rare, a juvenile form of this disease that presents in adolescence or early adulthood can result in epilepsy, mild developmental delay, and intellectual disability. Life expectancy is variable and no genotype-phenotype correlation has been reported.

For information about carrier frequency and residual risk, please see the residual risk table.