海南省少数民族地区脂肪酸氧化代谢病新生儿筛查结果分析

doi:10.12372/jcp.2024.22e1193

Abstract

Abstract:

Objective To investigate the incidence of fatty acid oxidative metabolism disorders (FAOD) in the neonatal population in ethnic minority areas of Hainan Province, and to analyse the clinical characteristics of the diagnosed children, so as to provide the basis for the prevention of birth defects in Hainan Province. Methods Tandem mass spectrometry screening data of newborns with inherited metabolic disorders from October 2016 to December 2021 were collected from ethnic minority areas in Hainan Province. Tandem mass spectrometry was used to detect the levels of free carnitine as well as 30 acylcarnitines in dried blood spots of newborns. Initial screen-positive neonates were recalled for review of blood tandem mass spectrometry, urinary organic acids were measured by gas-phase mass spectrometry, and peripheral blood was collected from neonates and their parents for gene sequencing. Results A total of 46285 newborn samples were screened, of which 513 were positive in the first screening, the positive rate of the first screening was 1/90, 501 cases were recalled, and 11 cases of fatty acid β -oxidation metabolic disease were diagnosed, the incidence rate was 1/4208, including 6 cases of primary carnitine deficiency, 1 case of short chain, medium chain and very long acyl-CoA dehydrogenase deficiency, and 1 case of carnitine palmitoyl transferase I and II deficiency. Conclusion The incidence of fatty acid β-oxidative metabolic disease is high among newborns in minority areas of Hainan province, and primary carnitine deficiency is more common. It is suggested that the screening of neonatal genetic metabolic diseases by tandem mass spectrometry should be included in the routine of newborn screening program.

Key words: fatty acid oxidative metabolic disease, tandem mass spectrometry, acyl carnitine, newborn screening

HUANG Cidan, XU Haizhu, WEN Yingmei, LIU Xiulian. Analysis of the results of newborn screening for fatty acid oxidative metabolic diseases in ethnic minority areas of Hainan Province[J].Journal of Clinical Pediatrics, 2024, 42(2): 133-138.

Figures/Tables 3

病例	性别	确诊年龄	末次随访年龄	治疗情况	随访情况
PCD	男	1月7天	4岁3月	左卡尼汀100~200 mg·kg^-1·d^-1保持C0在正常或接近正常水平	体格检查、智力发育、肝功能、心肌酶谱、心电图、彩色多普勒超声心动图未见异常
PCD	男	6月13天	4岁2月	左卡尼汀100~200 mg·kg^-1·d^-1保持C0在正常水平	体格检查、智力发育、肝功能、心肌酶谱、心电图、彩色多普勒超声心动图未见异常
PCD	男	1月18天	4岁	左卡尼汀100~200 mg·kg^-1·d^-1保持C0在正常水平	体格检查、智力发育、肝功能、心肌酶谱、心电图、彩色多普勒超声心动图未见异常
PCD	男	3月2天	3岁3月	左卡尼汀100~200 mg·kg^-1·d^-1保持C0在正常水平	体格检查、智力发育、肝功能、心肌酶谱、心电图、彩色多普勒超声心动图未见异常
PCD	男	3月15天	4岁4月	左卡尼汀100~200 mg·kg^-1·d^-1保持C0在正常水平	体格检查、智力发育、肝功能、心肌酶谱、心电图、彩色多普勒超声心动图未见异常
PCD	女	1岁1月	3岁11月	左卡尼汀100~200 mg·kg^-1·d^-1保持C0在正常或接近正常水平	1岁确诊，心肌受损、致密化不全，射血分数低，肝功能、心电图异常。经规律用药后，上述检测指标逐渐恢复正常
SCADD	女	3月9天	2岁7月	低脂肪饮食，避免饥饿、限制运动时间和强度，补充肉碱、维生素B₂	体格检查、智力发育、肝功能、心肌酶谱、心电图、彩色多普勒超声心动图未见异常
MCADD	男	3月6天	3岁6月	采用低脂肪饮食，避免饥饿、限制运动时间和强度，未用药物治疗	体格检查、智力发育、肝功能、心肌酶谱、心电图、彩色多普勒超声心动图未见异常
VLCADD	女	5月6天	5岁1月	高碳水化合物和低脂肪饮食，补充中链三酰甘油，避免饥饿、限制运动时间和强度	因“感冒、纳差、幼儿园运动时间长”出现昏迷，当地诊所输注葡萄糖后缓解。平素随访依从性差，体格检查、智力发育、肝功能、心肌酶谱、心电图、彩色多普勒超声心动图未见异常
CPTⅠ	女	6月3天	-	家长拒绝随访	失访
CPTⅡ	男	8月7天	4岁1月	高碳水化合物和低脂肪饮食，避免饥饿、限制运动时间和强度	体格检查、智力发育、肝功能、心肌酶谱、心电图、彩色多普勒超声心动图未见明显异常

References 27

[1]	El-Gharbawy A, Jerry V. Inborn errors of metabolism with myopathy: defects of fatty acid oxidation and the carnitine shuttle system[J]. Pediatr Clin North Am, 2018, 65(2): 317-335. doi: 10.1016/j.pcl.2017.11.006
[2]	Touati G, Gorce M, Oliver-Petit I, et al. New inborn errors of metabolism added in the French program of neonatal screening[J]. Med Sci (Paris), 2021, 37(5): 507-518. doi: 10.1051/medsci/2021057 pmid: 34003097
[3]	Kapoor S, Thelma BK. Status of newborn screening and inborn errors of metabolism in India[J]. Indian J Pediatr, 2018, 85(12): 1110-1117. doi: 10.1007/s12098-018-2681-5 pmid: 29736696
[4]	Zhang R, Qiang R, Song C, et al. Spectrum analysis of inborn errors of metabolism for expanded newborn screening in a northwestern Chinese population[J]. Sci Rep, 2021, 11(1): 2699. doi: 10.1038/s41598-021-81897-y pmid: 33514801
[5]	Longo N, Frigeni M, Pasquali M. Carnitine transport and fatty acid oxidation[J]. Biochim Biophys Acta, 2016, 1863(10): 2422-2435. doi: 10.1016/j.bbamcr.2016.01.023 pmid: 26828774
[6]	赵振东, 王洁, 谢曼芳, 等. 海南省少数民族自治市县原发性肉碱缺乏症筛查分析[J]. 中华检验医学杂志, 2019(4): 293-296.
[7]	温英梅, 赵振东, 王洁. 海南省黎族新生儿原发性肉碱缺乏症筛查及基因情况分析[J]. 中国全科医学, 2020, 23(18): 2299-2303. doi: 10.12114/j.issn.1007-9572.2020.00.293
[8]	Ferreira CR, Rahman S, Keller M, et al. An international classification of inherited metabolic disorders (ICIMD)[J]. J Inherit Metab Dis, 2021, 44(1): 164-177. doi: 10.1002/jimd.12348 pmid: 33340416
[9]	Burlina AB, Polo G, Salviati L, et al. Newborn screening for lysosomal storage disorders by tandem mass spectrometry in North East Italy[J]. J Inherit Metab Dis, 2018, 41(2): 209-219. doi: 10.1007/s10545-017-0098-3 pmid: 29143201
[10]	Frigeni M, Balakrishnan B, Yin X, et al. Functional and molecular studies in primary carnitine deficiency[J]. Hum Mutat, 2017, 38(12): 1684-1699. doi: 10.1002/humu.23315 pmid: 28841266
[11]	Lin W, Wang K, Zheng Z, et al. Newborn screening for primary carnitine deficiency in Quanzhou, China[J]. Clin Chim Acta, 2021, 512: 166-171. doi: 10.1016/j.cca.2020.11.005 pmid: 33181153
[12]	Nowinski SM, Solmonson A, Rusin SF, et al. Mitochondrial fatty acid synthesis coordinates oxidative metabolism in mammalian mitochondria[J]. Elife, 2020, 9: e58041. doi: 10.7554/eLife.58041
[13]	Raud B, McGuire PJ, Jones RG, et al. Fatty acid metabolism in CD8⁺ T cell memory: challenging current concepts[J]. Immunol Rev, 2018, 283(1): 213-231. doi: 10.1111/imr.2018.283.issue-1
[14]	Wilcken B, Wiley V, Hammond J, et al. Screening newborns for inborn errors of metabolism by tandem mass spectrometry[J]. N Engl J Med, 2003, 348(23): 2304-2312. doi: 10.1056/NEJMoa025225
[15]	Feuchtbaum L, Carter J, Dowray S, et al. Birth prevalence of disorders detectable through newborn screening by race/ethnicity[J]. Genet Med, 2012, 14(11): 937-945. doi: 10.1038/gim.2012.76 pmid: 22766612
[16]	Lindner M, Gramer G, Haege G, et al. Efficacy and outcome of expanded newborn screening for metabolic diseases--report of 10 years from South-West Germany[J]. Orphanet J Rare Dis, 2011, 6: 44. doi: 10.1186/1750-1172-6-44 pmid: 21689452
[17]	la Marca G, Malvagia S, Casetta B, et al. Progress in expanded newborn screening for metabolic conditions by LC-MS/MS in Tuscany: update on methods to reduce false tests[J]. J Inherit Metab Dis, 2008, 31 (Suppl 2): S395-S404.
[18]	Zhao Z, Chen C, Sun XS, et al. Newborn screening for inherited metabolic diseases using tandem mass spectrometry in China: outcome and cost-utility analysis[J]. J Med Screen, 2022, 29(1): 12-20. doi: 10.1177/09691413211021621
[19]	Sun F, Zhang JX, Yang CY, et al. The genetic characteristics of congenital hypothyroidism in China by comprehensive screening of 21 candidate genes[J]. Eur J Endocrinol, 2018, 178(6): 623-633. doi: 10.1530/EJE-17-1017 pmid: 29650690
[20]	Koizumi A, Nozaki J, Ohura T, et al. Genetic epidemiology of the carnitine transporter OCTN2 gene in a Japanese population and phenotypic characterization in Japanese pedigrees with primary systemic carnitine deficiency[J]. Hum Mol Genet, 1999, 8: 2247-2254. pmid: 10545605
[21]	Wilcken B, Wiley V, Sim KG, et al. Carnitine transporter defect diagnosed by newborn screening with electrospray tandem mass spectrometry[J]. J Pediatr, 2001, 138: 581-584. doi: 10.1067/mpd.2001.111813
[22]	Echaniz-Laguna A, Biancalana V, Gaignard P, et al. Primary carnitine deficiency in a 57-year-old patient with recurrent exertional rhabdomyolysis[J]. BMJ Case Rep, 2018, 2018: bcr2018224272.
[23]	Jakoby M 4th, Jaju A, Marsh A, et al. Maternal primary carnitine deficiency and a novel solute carrier family 22 member 5 (SLC22A5) mutation[J]. J Investig Med High Impact Case Rep, 2021, 9: 23247096211019543.
[24]	Lin Y, Zhang W, Huang C, et al. Increased detection of primary carnitine deficiency through second-tier newborn genetic screening[J]. Orphanet J Rare Dis, 2021, 16(1): 149. doi: 10.1186/s13023-021-01785-6 pmid: 33757571
[25]	Wang H, Wang X, Li Y, et al. Screening for inherited metabolic diseases using gas chromatography-tandem mass spectrometry (GC-MS/MS) in Sichuan, China[J]. Biomed Chromatogr, 2017, 31(4).
[26]	Yang Q, Xu L, Tang LJ, et al. Simultaneous detection of multiple inherited metabolic diseases using GC-MS urinary metabolomics by chemometrics multi-class classification strategies[J]. Talanta, 2018, 186: 489-496. doi: S0039-9140(18)30438-7 pmid: 29784392
[27]	杨池菊, 史彩虹, 周成, 等. 山东省济宁地区新生儿脂肪酸氧化代谢病筛查及随访分析[J]. 浙江大学学报(医学版), 2021, 50(4): 472-480.

病例	民族	C0	C2	C3	C3DC+ C4OH	C4	C4DC+ C5OH	C5	C6	C8	C10	C12	C14	C16	C18	其他异常指标
1	汉	2.39↓	2.26↓	0.27↓	0.01↓	0.03↓	0.03↓	0.01↓	0.01	0.01↓	0.01↓	0.01↓	0.04↓	0.56	0.15↓
2	汉	4.83↓	3.22↓	0.27↓	0.03	0.05↓	0.10	0.02↓	0.03	0.03	0.03	0.02	0.04↓	0.86	0.26↓
3	黎	2.17↓	0.59↓	0.1↓	0.01↓	0.02↓	0.04↓	0.01↓	0↓	0.01↓	0.01↓	0.01↓	0.01↓	0.12↓	0.1↓
4	汉	4.47↓	2.16↓	0.28↓	0.01↓	0.03↓	0.06↓	0.02↓	0.01	0.01↓	0.01↓	0.02	0.03↓	0.48	0.18↓
5	黎	3.14↓	1.98↓	0.29↓	0.02↓	0.03↓	0.06↓	0.03↓	0.01	0.01↓	0.02	0.02	0.04↓	0.80	0.23↓
6	汉	1.07↓	0.35↓	0.03↓	0.01↓	0.02↓	0.02↓	0.01↓	0↓	0.01↓	0.01↓	0.01↓	0.01↓	0.09↓	0.07↓
7	汉	32.83	12.61	1.54	0.04	1.17↑	0.19	0.16	0.05	0.04	0.05	0.05	0.10	0.79	0.26↓
8	汉	39.10	15.33	3.12	0.04	0.13	0.21	0.25	1.26↑	12.85	0.39	0.25	0.16	2.96	1.35
9	汉	28.98	9.94	1.72	0.03	0.09	0.28	0.08	0.02	0.02	0.04	0.14	1.01↑	2.38	1.64	C14:1 (1.59↑)
10	黎	65.34	11.58	1.69	0.11	0.22	0.37	0.06	0.03	0.02	0.02	0.02	0.05↓	0.16↓	0.12↓
11	黎	24.11	12.38	1.03	0.16	0.19	0.44↑	0.08	0.02	0.02	0.02	0.29↑	0.86↑	6.68↑	1.91↑	(C16+ C18:1)/ C2(0.42↑)

病种	基因	变异1		变异2		纯合/ 复合杂合
病种	基因	核苷酸改变	氨基酸改变	核苷酸改变	氨基酸改变	纯合/ 复合杂合
PCD	SLC22A5	c.760C>T	p.Arg254*	c.51C>G	p.Phe17Leu	复合杂合
PCD	SLC22A5	c.760C>T	p.Arg254*	c.1400C>G	p.Ser467Cys	复合杂合
PCD	SLC22A5	c.760C>T	p.Arg254*	c.51C>G	p.Phe17Leu	复合杂合
PCD	SLC22A5	c.760C>T	p.Arg254*	c.760C>T	p.Arg254*	纯合
PCD	SLC22A5	c.51C>G	p.Phe17Leu	c.51C>G	p.Phe17Leu	纯合
PCD	SLC22A5	c.51C>G	p.Phe17Leu	c.51C>G	p.Phe17Leu	纯合
SCADD	ACADS	c.889C>T	p.Arg297Cys	c.256G>A	p.Glu86Lys	复合杂合
MCADD	ACADM	c.1097G>A	p.Gly366Glu	c.1097G>A	p.Gly366Glu	纯合
VLCADD	ACADVL	c.664G>A	p.Gly222Arg	c.1819T>G	p.Cys607Gly	复合杂合
CPTⅠ	CPT1A	c.1163+4C>T	-	c.1163+4C>T	-	纯合
CPTⅡ	CPT2	c.1408G>T	p.Ala470Ser	c.1102G>A	p.Val368Ile	复合杂合

Analysis of the results of newborn screening for fatty acid oxidative metabolic diseases in ethnic minority areas of Hainan Province

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