Phosphoserine aminotransferase deficiency diagnosed by whole‐exome sequencing and LC–MS/MS reanalysis: A case report and review of literature

Background Phosphoserine aminotransferase deficiency (PSATD) is an autosomal recessive disorder associated with hypertonia, psychomotor retardation, and acquired microcephaly. Patients with PSATD have low concentrations of serine in plasma and cerebrospinal fluid. Methods We reported a 2‐year‐old female child with developmental delay, dyskinesia, and microcephaly. LC–MS/MS was used to detect amino acid concentration in the blood and whole‐exome sequencing (WES) was used to identify the variants. PolyPhen‐2 web server and PyMol were used to predict the pathogenicity and changes in the 3D model molecular structure of protein caused by variants. Results WES demonstrated compound heterozygous variants in PSAT1, which is associated with PSATD, with a paternal likely pathogenic variant (c.235G>A, Gly79Arg) and a maternal likely pathogenic variant (c.43G>C, Ala15Pro). Reduced serine concentration in LC–MS/MS further confirmed the diagnosis of PSATD in this patient. Conclusions Our findings demonstrate the importance of WES combined with LC–MS/MS reanalysis in the diagnosis of genetic diseases and expand the PSAT1 variant spectrum in PSATD. Moreover, we summarize all the cases caused by PSAT1 variants in the literature. This case provides a vital reference for the diagnosis of future cases. We reported a 2‐year‐old female child with developmental delay, dyskinesia, and microcephaly. The patient was eventually diagnosed as PSATD by WES combined with LC–MS/MS reanalysis. This case provides a vital reference for the diagnosis of future genetic disease cases.