C4OH is a potential newborn screening marker—a multicenter retrospective study of patients with beta-ketothiolase deficiency in China

Orphanet Journal of Rare Diseases

Dongjuan Wang¹  Zhantao Yang²  Huiming Yan³  Xinwen Huang⁴  Yiming Lin⁵  Yuanyuan Kong⁶  Chiju Yang⁷  Mingfang Liu⁸  Yun Sun⁹  Haili Hu^1,10  Yuyan Shen^1,11  Tingting Niu^1,12  Xiaole Li^1,13  Haiyan He^1,14 

[1] Center for Clinical Molecular Medicine/Newborn Screening Center, Children’s Hospital, Chongqing Medical University, Chongqing, China;Continuing Medical Education and Research Center, Dian Diagnostics Group Co., Ltd, 329 Jinpeng Street, Xihu District, 310030, Hangzhou, China;Department of Genetic Medicine, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, China;Department of Genetics and Metabolism, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Binsheng Road, 310052, Hangzhou, China;Department of Genetics and Metabolism, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Binsheng Road, 310052, Hangzhou, China;Neonatal Disease Screening Center, Quanzhou Maternity and Children’s Hospital, Quanzhou, China;Department of Newborn Screening, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, 251 Yaojiayuan Road, Chaoyang District, 100026, Beijing, China;Jining Maternal and Child Health Family Service Center, Jining, China;Liaocheng Maternal and Child Health Hospital, Shandong, China;Nanjing Maternity and Child Health Care Hospital, Women’s Hospital of Nanjing Medical University, Jiangsu, China;Neonatal Disease Screening Center, Hefei Maternal and Child Health, Family Planning Service Center, Anhui, China;Neonatal Disease Screening Center, Huaihua Maternal and Child Health Hospital, Huaihua, China;Shandong Provincial Maternal and Child Health Care Hospital, Shandong, China;Third Affiliated Hospital of Zhengzhou University, Henan, China;Wuhu Maternal and Child Health Family Planning Service Center, Anhui, China;

关键词: Beta-ketothiolase deficiency;    Chinese;    Newborn screening;    ACAT1;    Isoleucine catabolism;   

DOI  :  10.1186/s13023-021-01859-5

来源: Springer

【 摘 要 】

BackgroundBeta-ketothiolase deficiency (BKTD) is an autosomal recessive disorder caused by biallelic mutation of ACAT1 that affects both isoleucine catabolism and ketolysis. There is little information available regarding the incidence, newborn screening (NBS), and mutational spectrum of BKTD in China.ResultsWe collected NBS, biochemical, clinical, and ACAT1 mutation data from 18 provinces or municipalities in China between January 2009 and May 2020, and systematically assessed all available published data from Chinese BKTD patients. A total of 16,088,190 newborns were screened and 14 patients were identified through NBS, with an estimated incidence of 1 per 1 million newborns in China. In total, twenty-nine patients were genetically diagnosed with BKTD, 12 of which were newly identified. Most patients exhibited typical blood acylcarnitine and urinary organic acid profiles. Interestingly, almost all patients (15/16, 94%) showed elevated 3-hydroxybutyrylcarnitine (C4OH) levels. Eighteen patients presented with acute metabolic decompensations and displayed variable clinical symptoms. The acute episodes of nine patients were triggered by infections, diarrhea, or an inflammatory response to vaccination. Approximately two-thirds of patients had favorable outcomes, one showed a developmental delay and three died. Twenty-seven distinct variants were identified in ACAT1, among which five were found to be novel.ConclusionThis study presented the largest series of BKTD cohorts in China. Our results indicated that C4OH is a useful marker for the detection of BKTD. The performance of BKTD NBS could be improved by the addition of C4OH to the current panel of 3-hydroxyisovalerylcarnitine and tiglylcarnitine markers in NBS. The mutational spectrum and molecular profiles of ACAT1 in the Chinese population were expanded with five newly identified variants.

【 授权许可】

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