Diagnosis of delayed propionic acidemia and identification of one novel mutation

Abstract

Objective To investigate the clinical characteristics and gene mutations of delayed propionic academia (PA). Methods One male patient with delayed PA who was hospitalized in Nanjing Maternity and Child Health Care Hospital on May 20, 2016, was chosen as study object. The clinical data of the patient was analyzed retrospectively, including results of tandem mass spectrometry (MS/MS) detection, gas chromatography-mass spectrometry (GC/MS) detection, and clinical manifestations. The DNA was extracted from the blood samples of child and his parents, and the Panel high-throughput sequencing technology was used to amplify the mutations. The study protocol was approved by the Ethnical Review Board of Investigation in Human Beings of Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University. Results ① There were no specific clinical symptoms of this patient. The concentration of propionyl carnitine (C3) ranged from 2.79-7.03 μmol/L, urine 3-hydroxy propionic acid ranged from 0-129.48 μmol/L. ②Two mutations (c.802C>T, c. 827delG) in PCCA gene were confirmed. The gene detection results showed these two mutations were inherited from father [c.827delG(p.Gly276ValfsX46)] and mother [c.802C>T(p.Arg268Cys)], respectively. The frameshift mutation in PCCA gene (c.827delG) was novel. ③ The follow-up results of liver function and renal function showed normal. Conclusions It is important to use a combination of MS/MS, GC/MS and Panel high-throughput sequencing technology in the diagnosis of delayed PA. The mutation c. 827delG is a specific novel mutation of PCCA gene, expanding its mutation spectrum. Key words: Propionic acidemia; Genes; Tandem mass spectrometry; Gas chromatography-mass spectrometry; Child