Mild phenotypes of phosphoglycerate dehydrogenase deficiency by a novel mutation of PHGDH gene: Case report and literature review

• Published in: International journal of developmental neuroscience 2023-02, Vol.83 (1), p.44-52
• Main Authors: Fu, Junyi, Chen, Liqing, Su, Tangfeng, Xu, Sanqing, Liu, Yan
• Format: Article
• Language: English
• Subjects: developmental delay; Humans; microcephaly; Microcephaly - diagnostic imaging; Microcephaly - genetics; Mutation - genetics; Phenotype; PHGDH gene; Phosphoglycerate Dehydrogenase - genetics; seizures; Seizures - diagnostic imaging; Seizures - genetics; Serine - genetics; serine deficiency
• ISSN: 0736-5748; 1873-474X
• DOI: 10.1002/jdn.10236

Phosphoglycerate dehydrogenase (PHGDH) deficiency is a rare autosomal recessive genetic disease of serine biosynthesis. Its typical features are congenital microcephaly, epileptic seizures, and psychomotor developmental delay. Here, we reported the first Chinese familial cases with genetically confirmed PHGDH deficiency and reviewed several previous reports. Two siblings in this family presented with microcephaly, psychomotor retardation, and epilepsy in early juvenile. Brain magnetic resonance imaging (MRI) showed only a slight change of enlarged ventricle. Biochemical investigations revealed low serum serine and glycine concentrations. The whole‐exome sequencing (WES) results identified a missense variant in the PHGDH gene (NM_006623.4: exon11: c.1211T>A, p. Val404Asp). Although two patients in this Chinese family carried the same pathogenic mutation in the PHGDH, their symptoms and responses to treatment were not exactly the same. We found a novel variant in the PHGDH gene and expanded the genotypic and phenotypic spectrum of serine biosynthesis disorders. We reported a novel pathogenic mutation in the PHGDH gene (c.1211T>A, p. Val404Asp) of serine biosynthesis disorders; in our case, patients had microcephaly, psychomotor retardation, seizures, and low serine concentrations, but brain magnetic resonance imaging (MRI) showed only a slight change.