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J Zhejiang Univ (Med Sci)  2021, Vol. 50 Issue (4): 472-480    DOI: 10.3724/zdxbyxb-2021-0259
Screening and follow-up results of fatty acid oxidative metabolism disorders in 608 818 newborns in Jining, Shandong province
YANG Chiju1(),SHI Caihong2,ZHOU Cheng1,WAN Qiuhua1,ZHOU Yanbin1,CHEN Xigui1,JIN Xianlian1,HUANG Chenggang3,XU Peng1,*()
1. Neonatal Disease Screening Center, Jining Maternal and Child Health and Family Planning Service Center, Jining 272000, Shandong Province, China;
2. Clinical Laboratory, Jining Second People’s Hospital, Jining 272000, Shandong Province, China;
3. Zhejiang Bosheng Biotechnology Co., Ltd., Hangzhou 310012, China
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Objective:To investigate the incidence and gene mutation characteristics of fatty acid oxidative metabolism disorders in Jining area of Shandong province , and to evaluate the therapeutic effect.Methods: Blood samples of newborns were collected in Jining of Shandong province between July 14, 2014 and December 31, 2019. Tandem mass spectrometry was used to determine the levels of carnitine and acylcarnitine in the blood to screen for fatty acid oxidative metabolism disorder. For newborns with positive screening result, blood DNA was analyzed by MassARRAY and high-throughput sequencing, then verified by Sanger sequencing. The diagnosed children were given early intervention and treatment, and followed up. Results:Forty-two children with fatty acid oxidative metabolism disorders were screened out of 608 818 newborns, with an incidence rate of 1/14 496. Primary carnitine deficiency (16 cases, 38.10%) and short-chain acyl-CoA dehydrogenase deficiency (16 cases, 38.10%) were the most common, followed by very long-chain acyl-CoA dehydrogenase deficiency (6 cases, 14.29%), medium-chain acyl-CoA dehydrogenase deficiency (4 cases, 9.53%). In children with primary carnitine deficiency, c.1400C>G (p.S467C) and c.51C>G (p.F17L) were the most common inSLC22A5 mutations; and c.278C>T (p.S93L), c.1049T >C (p.L350P), c.572A>G (p.K191R), c.431T>C (p.L144P) were newly discovered mutations. Ten children with carnitine replacement therapy showed normal development during the follow-up. In 6 children without carnitine replacement treatment, hypoglycemia developed during the neonatal period in 1 case, in whom the creatine kinase was increased, and the intellectual and language development delayed in the later period; the other 5 children developed normally during the follow-up period. TheACADS gene mutations c.1031A>G (p.E344G) and c.164C>T (p.P55L) were common in children with short-chain acyl-CoA dehydrogenase deficiency, and the children developed normally during the follow-up. In children with very long-chain acyl-CoA dehydrogenase deficiency, the c.1349G>A (p.R450H) was common inACADVL gene mutations; and c.488T>A (p.L163*), c.1228G>T (p.D410Y), c.1276G>A (p.A426T), c.1522C>T (p.Q508*), c.1226C>T (p.T409M) were newly discovered mutations. Three children treated with milk powder rich in medium-chain fatty acids had normal development during the follow-up. The other 3 cases with combined carnitine reduction were treated with levocarnitine and milk powder enriched of medium-chain fatty acids, 1 case developed normally during the follow-up, 1 case died of acute illness at the age of 3?months, and 1 case had acute illness and recovered after treatment, and developed normally during the follow-up. c.449_452del (p.T150Rfs*4) was the most commonACADM gene mutation in children with medium-chain acyl-CoA dehydrogenase deficiency, and c. 718A>G (p.M240V) was a newly discovered mutation. All children received low-fat diet, and hunger and fatigue were avoided; 1 child was supplemented with L-carnitine, and the other 3 children were not treated with drugs, and all of them developed normal during the follow-up.Conclusions:Primary carnitine deficiency and short-chain acyl-CoA dehydrogenase deficiency are the most common fatty acid oxidative metabolism disorders in Jining area. There are gene hotspot mutations and new discovered gene mutations in patients. Patients with early diagnosis and treatment through neonatal screening have a good prognosis.

Key wordsLipid metabolism, inborn errors      Gene mutation      Tandem mass spectrometry      Neonatal screening      Follow-up studies     
Received: 26 April 2021      Published: 01 November 2021
CLC:  R596  
Corresponding Authors: XU Peng     E-mail:;
Cite this article:

YANG Chiju,SHI Caihong,ZHOU Cheng,WAN Qiuhua,ZHOU Yanbin,CHEN Xigui,JIN Xianlian,HUANG Chenggang,XU Peng. Screening and follow-up results of fatty acid oxidative metabolism disorders in 608 818 newborns in Jining, Shandong province. J Zhejiang Univ (Med Sci), 2021, 50(4): 472-480.

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关键词: 脂质代谢缺陷, 先天性,  基因突变,  串联质谱法,  新生儿筛查,  随访研究 
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