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Medium-chain acyl-CoA dehydrogenase deficiency: neonatal screening and follow-up
TONG Fan, JIANG Ping-Ping, YANG Ru-Lai, HUANG Xiao-Lei, ZHOU Xue-Lian, HONG Fang, QIAN Gu-Ling, ZHAO Zheng-Yan, SHU Qiang
Chinese Journal of Contemporary Pediatrics ›› 2019, Vol. 21 ›› Issue (1) : 52-57.
PDF(1634 KB)
PDF(1634 KB)
Medium-chain acyl-CoA dehydrogenase deficiency: neonatal screening and follow-up
Objective To investigate the epidemiological characteristics, phenotype, genotype, and prognosis of medium-chain acyl-CoA dehydrogenase deficiency (MCADD) in the Chinese population. Methods A retrospective analysis was performed for the clinical data of the neonates who underwent screening with high-performance liquid chromatography-tandem mass spectrometry from January 2009 to June 2018 and were diagnosed with MCADD by gene detection. Results A total of 2674835 neonates underwent neonatal screening, among whom 12 were diagnosed with MCADD. Gene detection was performed for 10 neonates with MCADD and found 13 mutation types at 16 mutation sites of the ACADM gene, among which there were 7 reported mutations (p.T150Rfs*4, p.M1V, p.R206C, p.R294T, p.G310R, p.M328V, and p.G362E), 5 novel mutations (p.N194D, p.A324P, p.N366S, c.118+3A > G, and c.387+1del G), and 1 exon 11 deletion; p.T150Rfs*4 was the most common mutation (4/16). The detection rate of mutation sites in the ACADM gene was 80%. No phenotype-genotype correlation was observed. Dietary guidance and symptomatic treatment were given after confirmed diagnosis. No acute metabolic imbalance was observed within 4-82 months of follow-up. All neonates had good prognosis except one who had brain dysplasia. Conclusions MCADD is relatively rare in southern China, and p.T150Rfs*4 is a common mutation in the Chinese population. Cases with positive screening results should be evaluated by octanoylcarnitine C8 value and gene detection.
Medium-chain acyl-CoA dehydrogenase / Prevalence rate / Genotype / Neonate
[1] Kølvraa S, Gregersen N, Christensen E, et al. In vitro fibroblast studies in a patient with C6-C10-dicarboxylic aciduria:evidence for a defect in general acyl-CoA dehydrogenase[J]. Clin Chim Acta, 1982, 126(1):53-67.
[2] Matern D, Rinaldo P. Medium-chain acyl-coenzyme A dehydrogenase deficiency[M]//GeneReviews:Genetic Disease Online Reviews at GeneTests-GeneClinics. Seattle:University of Washington, 2015.
[3] Oerton J, Khalid JM, Besley G, et al. Newborn screening for medium chain acyl-CoA dehydrogenase deficiency in England:prevalence, predictive value and test validity based on 1.5 million screened babies[J]. J Med Screen, 2011, 18(4):173-181.
[4] Chien YH, Lee NC, Chao MC, et al. Fatty acid oxidation disorders in a chinese population in Taiwan[J]. JIMD Rep, 2013, 11:165-172.
[5] Matern D. Acylcarnitines[M]//Blau N, Duran M, Gibson KM, et al. Physician's Guide to the Diagnosis, Treatment, and Followup of Inherited Metabolic Diseases. Heidelberg:SpringerVerlag, 2014:775-784.
[6] Hall PL, Wittenauer A, Hagar A. Newborn screening for medium chain acyl-CoA dehydrogenase deficiency:performance improvement by monitoring a new ratio[J]. Mol Genet Metab, 2014, 113(4):274-277.
[7] Lindner M, Hoffmann GF, Matern D. Newborn screening for disorders of fatty-acid oxidation:experience and recommendations from an expert meeting[J]. J Inherit Metab Dis, 2010, 33(5):521-526.
[8] Rinaldo P. Retrospective and prospective date mining to develop continuous, covariate-adjusted reference and disease percentiles for biomarkers of metabolic disease[J]. Clin Chem Lab Med, 2017, 55:1200-1201.
[9] Gregersen N, Kølvraa S, Rasmussen K, et al. General (mediumchain) acyl-CoA dehydrogenase deficiency (non-ketotic dicarboxylic aciduria):quantitative urinary excretion pattern of 23 biologically significant organic acids in three cases[J]. Clin Chim Acta, 1983, 132(2):181-191.
[10] Al-Hassnan ZN, Imtiaz F, Al-Amoudi M, et al. Medium-chain acyl-CoA dehydrogenase deficiency in Saudi Arabia:incidence, genotype, and preventive implications[J]. J Inherit Metab Dis, 2010, 33(Suppl 3):S263-S267.
[11] Shigematsu Y, Hirano S, Hata I, et al. Newborn mass screening and selective screening using electrospray tandem mass spectrometry in Japan[J]. J Chromatogr B Analyt Technol Biomed Life Sci, 2002, 776(1):39-48.
[12] Ensenauer R, Winters JL, Parton PA, et al. Genotypic differences of MCAD deficiency in the Asian population:novel genotype and clinical symptoms preceding newborn screening notification[J]. Genet Med, 2005, 7(5):339-343.
[13] Janzen N, Hofmann AD, Schmidt G, et al. Non-invasive test using palmitate in patients with suspected fatty acid oxidation defects:disease-specific acylcarnitine patterns can help to establish the diagnosis[J]. Orphanet J Rare Dis, 2017, 12(1):187.
[14] Piercy H, Machaczek K, Ali P, et al. Parental experiences of raising a child with medium chain acyl-CoA dehydrogenase deficiency[J]. Glob Qual Nurs Res, 2017, 4:2333393617707080.
[15] Derks TG, Van Spronsen FJ, Rake JP, et al. Safe and unsafe duration of fasting for children with MCAD deficiency[J]. Eur J Pediatr, 2007, 166(1):5-11.
[16] Dessein AF, Fontaine M, Andresen BS, et al. A novel mutation of the ACADM gene (c.145C>G) associated with the common c.985A>G mutation on the other ACADM allele causes mild MCAD deficiency:a case report[J]. Orphanet J Rare Dis, 2010, 5:26.
