60 例丙酸血症患者表型与基因型关系分析：三级医院 14 年经验。
Analysis of the relationship between phenotypes and genotypes in 60 Chinese patients with propionic acidemia: a fourteen-year experience at a tertiary hospital.
机构信息
Department of Pediatrics, Peking University First Hospital, Beijing, 100034, China.
Department of Clinical Laboratory, China-Japan Friendship Hospital, Beijing, 100029, China.
出版信息
Orphanet J Rare Dis. 2022 Mar 24;17(1):135. doi: 10.1186/s13023-022-02271-3.
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.
背景
丙酸血症是一种严重的遗传性代谢紊乱，由编码丙酰辅酶 A 羧化酶的 PCCA 和 PCCB 基因缺陷引起。本研究旨在探讨中国人群中的临床特征和结局、分子流行病学以及表型-基因型关系。
方法
我们对 2007 年至 2020 年在北京大学生第一医院诊断的 60 例中国患者进行了回顾性研究。回顾了他们的临床和实验室数据。对 58 例患者的血液样本进行了下一代测序。
结果
仅 5 例（8.3%）通过新生儿筛查发现。在其余 55 例患者中，25 例为早发型（≤3 个月）疾病，30 例为晚发型（>3 个月）疾病。神经功能障碍是最常见的并发症。5 例通过新生儿筛查发现的患者基本发育正常。我们的队列中有 9 例（15%）死亡。24 例（41.4%）患者携带 PCCA 变异体，34 例（58.6%）患者携带 PCCB 变异体。在 PCCA 中鉴定出 30 个（11 个已报道和 19 个新）变异体，在 PCCB 中鉴定出 28 个（18 个已报道和 10 个新）变异体。该队列中最常见的变异体是 PCCA 中的 c.2002G>A 和 c.937C>T，以及 PCCB 中的 c.838dupC，频率分别为 13.9%（6/44 等位基因）、13.9%（6/44 等位基因）和 12.5%（8/64 等位基因）。PCCA 和 PCCB 变异体患者的临床特征和结局无差异。某些高频率和纯合子的变异体可能与早发型或晚发型丙酸血症有关。
结论
尽管基因型-表型相关性仍不清楚，但某些变异体似乎与早发型或晚发型丙酸血症有关。本研究进一步阐明了丙酸血症的复杂临床表现，并扩展了与丙酸血症相关的基因变异谱。
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