Analysis of gene mutation characteristics of medium chain acyl-CoA dehydrogenase deficiency by neonatal screening

SUN Ying-mei; YU Chun-dong; LYU Jin-feng; LYU Ya-nan; LI Wen-jie

doi:10.11852/zgetbjzz2018-1578

PDF(629 KB)

Chinese Journal of Child Health Care ›› 2019, Vol. 27 ›› Issue (10) : 1071-1074. DOI: 10.11852/zgetbjzz2018-1578

Analysis of gene mutation characteristics of medium chain acyl-CoA dehydrogenase deficiency by neonatal screening

SUN Ying-mei, YU Chun-dong, LYU Jin-feng, LYU Ya-nan, LI Wen-jie

Author information +

History +

Abstract

Objective To investigate the prevalence,clinical and gene mutation characteristics of medium chain acyl-CoA dehydrogenase deficiency(MCADD) in neonates in Qingdao area. Methods The acylcarnitine levels in the blood of 278 180 neonates from newborns screening program in Qingdao area were measured by tandem mass spectrometry.from January 2015 to August 2018.The suspected MCADD neonates were diagnosed by retrospective analysis of the urine organic acids and medium chain acyl-CoA dehydrogenase(ACADM) gene mutation. Results Four cases were diagnosed with MCADD,with the prevalence rate of 0.001 4%(1/69 545).There was no obvious abnormality in clinical manifestations,and the levles of medium chain acyl carnitine(C6-C10) increased in the four patients.Seven different mutations in the ACADM gene were identified in four cases.And one case was homozygous mutation:c.1 040G>T(p.G347V)/ c.1 040G>T(p.G347V).The other three cases were detected with compound heterozygous mutations,including c.157C>T(p.R53C)/ c.709-1G>A,c.1085G>A(p.G362E)/ c.461T>G(p.L154W)and c.587G>A(p.G196E)/ c.387+1delG.One case had increasing levels of 4-hydroxyphenylacetic acid and 4-hydroxyphenylpyruvate and hepatic insufficiency.Dietary guidance was given to the MCADD patients.No clinical symptoms were manifested and physical and intellectual development were normal during the follow-up period. Conclusion Inherited metabolic disease screening by tandem mass spectrometry for neonatal screening combined with gene detection can help early diagnosis of MCADD,which is of great significance to prevent the arrest of disease and improve the quality of life in MCADD children.

Key words

medium chain acyl-CoA dehydrogenase deficiency / tandem mass spectrometry / gene mutation

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

SUN Ying-mei, YU Chun-dong, LYU Jin-feng, LYU Ya-nan, LI Wen-jie. Analysis of gene mutation characteristics of medium chain acyl-CoA dehydrogenase deficiency by neonatal screening[J]. Chinese Journal of Child Health Care. 2019, 27(10): 1071-1074 https://doi.org/10.11852/zgetbjzz2018-1578

References

[1] Karaceper MD,Chakraborty P,Coyle D,et al.The health system impact of false positive newborn screening results for medium chain acyl-CoA dehydrogenase deficiency:a cohort study[J] .Orphanet J Rare Dis,2016,11:12.
[2] Gramer G,Haege G,Fang-Hoffmann J,et a1.Medium chain acyl-CoA dehydrogenase deficiency:evaluation of genotype-phenotype correlation in patients detected by newborn screening[J] .JIMD Rep,2015,23:101-112.
[3] Andresen BS,Lund AM,Hougaard DM,et a1.MCAD deficiency in Denmark[J] .Mol Genet Metab,2012,106(2):175-188.
[4] 顾学范.临床遗传代谢病[M].北京:人民卫生出版社,2015:146-149.
[5] Khalid JM,Oerton J,Besley G,et al.Relationship of octanoylcarnitine concentrations to age at sampling in unaffected newborns screened for medium-chain acyl-CoA dehydrogenase deficiency[J] .Clin Chem,2010,566(6):1015-1021.
[6] Leydiker KB,Neidich JA,Lorey F,et a1.Maternal medium chain acyl-CoA dehydrogenase deficiency identified by newborn screening[J] .Mol Genet Metab,2011,103(1):92-95.
[7] 姜涛,欧阳文献,谭艳芳,等.中链酰基辅酶A 脱氢酶缺乏症1例肝脏病理分析及基因检测[J] .临床儿科杂志,2016,34(4):249-252.
[8] 李甫棒,黄晓磊,陈洁,等.以黄疸为首发症状中链酰基辅酶A 脱氢酶缺乏症1 例报告[J] .临床儿科杂志,2010,28(9):880-881.
[9] 王立娜,任常军,李云,等.中链酰基辅酶A 脱氢酶缺乏症合并先天性心脏病1 例[J] .河北医药,2011,33(22):3520.
[10] Grünert SC,Wehrle A,Villavicencio-Lorini P,et a1.Medium chain acyl-CoA dehydrogenase deficiency associated with a novel splice mutation in the ACADM gene missed by newborn screening[J] .BMC Med Genet,2015,16:56.
[11] Touw CM,Smit GP,de Vries M,et a1.Risk stratification by residual enzyme activity after newborn screening for medium chain acyl-CoA dehydrogenase deficiency:data from a cohort study[J] .Orphanet J Rare Dis,2012,7:30.
[12] Derks TG,Touw CM,Ribas GS,et al.Experimental evidence for protein oxidative damage and altered antioxidant defense in patients with medium chain acyl-CoA dehydrogenase deficiency[J] .J Inherit Metab Dis,2014,37(5):783-789.
[13] Feillet F,Ogier H,Cheillan D,et a1.Medium chain acyl-CoA dehydrogenase(MCAD)deficiency:French consensus for neonatal screening,diagnosis and management[J] .Arch Pediatr,2012,19(2):184-193.
[14] Couce ML,Sánchez-Pintos P,Diogo L,et a1.Newborn scr eening for medium chain acyl-CoA dehydrogenase deficiency:regional experience and high incidence of carnitine deficiency[J] .Orphanet J Rare Dis,2013,8:102.