Molecular pathology report of late⁃onset propionic acidemia in adults: one case report and literature review

Abstract

Objective To report the first case of adult late⁃onset propionic acidemia (PA) caused by PCCB gene mutation in China, and summary the clinical and molecular pathological characteristics of patients with late⁃onset propionic acidemia. Methods and Results The clinical manisfestions of an eighteen⁃year⁃old male patient were acute onset of symmetrical injury at bilateral basal ganglia which induced metabolic encephalopathy with involuntury movement. Tandem mass spectrometry (MS/MS) test results of dried blood spots indicated that propionyl carnitine (C3) was 10.37 μmol/L, and the ratio of propionyl carnitine to acetyl carnitine (C3/C2) was 0.69. Gas chromatography⁃mass spectrometry (GC/MS) test results indicated urine 3⁃hydroxypropionic acid was 18 μmol/L, methyl citrate level was 12.70 μmol/L. The gene results detected a homozygous pathogenic mutation (exon 10: c.1087T＞C, p.Ser363Pro) in the PCCB gene. His parents had a heterozygous mutation in PCCB gene exon 10 c.1087T＞C (p.Ser363Pro), which was consistent with the phenomenon of family co⁃segregation, and the mutation site was consistent with a suspected pathogenic variant. The final molecular pathological diagnosis was late⁃onset propionic acidemia. Following the protein restriction diet, high⁃dose L⁃carnitine injection, and ammonia⁃lowering treatment, the dried blood spots propionic acid level and the urine 3⁃hydroxypropionic acid level decreased significantly. Conclusions The mutation exon c.1087T＞ C (p.Ser363Pro) is a rare and highly suspected pathogenic mutation of PCCB gene. MS/MS and GC/MS detection combined with whole exome sequencing technology is very important in the diagnosis of late⁃onset propionic acidemia.

doi：10.3969/j.issn.1672⁃6731.2021.04.010