Orphanet Journal of Rare Diseases (Mar 2022)

Analysis of the relationship between phenotypes and genotypes in 60 Chinese patients with propionic acidemia: a fourteen-year experience at a tertiary hospital

  • Yi Liu,
  • Zhehui Chen,
  • Hui Dong,
  • Yuan Ding,
  • Ruxuan He,
  • Lulu Kang,
  • Dongxiao Li,
  • Ming Shen,
  • Ying Jin,
  • Yao Zhang,
  • Jinqing Song,
  • Yaping Tian,
  • Yongtong Cao,
  • Desheng Liang,
  • Yanling Yang

DOI
https://doi.org/10.1186/s13023-022-02271-3
Journal volume & issue
Vol. 17, no. 1
pp. 1 – 13

Abstract

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Abstract Background Propionic acidemia is a severe inherited metabolic disorder, caused by the deficiency of propionyl-CoA carboxylase which encoded by the PCCA and PCCB genes. The aim of the study was to investigate the clinical features and outcomes, molecular epidemiology and phenotype-genotype relationship in Chinese population. Methods We conducted a retrospective study of 60 Chinese patients diagnosed at Peking University First Hospital from 2007 to 2020. Their clinical and laboratory data were reviewed. The next-generation sequencing was conducted on blood samples from 58 patients. Results Only 5 (8.3%) patients were identified by newborn screening. In the rest 55 patients, 25 had early-onset (≤ 3 months) disease and 30 had late-onset (> 3 months) disease. Neurological abnormalities were the most frequent complications. Five cases detected by newborn screening had basically normal development. Nine (15%) cases died in our cohort. 24 patients (41.4%) harbored PCCA variants, and 34 (58.6%) harbored PCCB variants. 30 (11 reported and 19 novel) variants in PCCA and 28 (18 reported and 10 novel) variants in PCCB mere identified. c.2002G>A and c.937C>T in PCCA, and c.838dupC in PCCB were the most common variants in this cohort, with the frequency of 13.9% (6/44 alleles), 13.9% (6/44 alleles) and 12.5% (8/64 alleles), respectively. There was no difference in clinical features and outcomes between patients with PCCA and PCCB variants. Certain variants with high frequencies and homozygotes may be associated with early-onset or late-onset propionic acidemia. Conclusions Although the genotype–phenotype correlation is still unclear, certain variants seemed to be related to early-onset or late-onset propionic acidemia. Our study further delineated the complex clinical manifestations of propionic acidemia and expanded the spectrum of gene variants associated with propionic acidemia.

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