{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T06:17:36Z","timestamp":1769149056220,"version":"3.49.0"},"reference-count":20,"publisher":"Walter de Gruyter GmbH","issue":"5","funder":[{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2020J01130"],"award-info":[{"award-number":["2020J01130"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Youth Research Project in the Health System of Fujian Province","award":["2020QNA083"],"award-info":[{"award-number":["2020QNA083"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,5,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec id=\"j_jpem-2020-0689_abs_001\">\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p> Multiple acyl-CoA dehydrogenase deficiency (MADD) is an autosomal recessive disorder of fatty acid, amino acid and choline metabolism. Late-onset MADD is caused by <jats:italic>ETFDH<\/jats:italic> mutations and is the most common lipid storage myopathy in China. However, few patients with MADD have been identified through newborn screening (NBS). This study assessed the acylcarnitine profiles and molecular features of patients with MADD identified through NBS.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jpem-2020-0689_abs_002\">\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p> From January 2014 to June 2020, 479,786 newborns screened via tandem mass spectrometry were recruited for this study. Newborns with elevated levels of multiple acylcarnitines were recalled, those who tested positive in the reassessment were referred for genetic analysis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jpem-2020-0689_abs_003\">\n                  <jats:title>Results<\/jats:title>\n                  <jats:p> Of 479,786 newborns screened, six were diagnosed with MADD. The MADD incidence in the Chinese population was estimated to be 1:79,964. Initial NBS revealed five patients with typical elevations in the levels of multiple acylcarnitines; however, in one patient, acylcarnitine levels were in the normal reference range during recall. Notably, one patient only exhibited a mildly increased isovalerylcarnitine (C5) level at NBS. The patient with an atypical acylcarnitine profile was diagnosed with MADD by targeted gene sequencing. Six distinct <jats:italic>ETFDH<\/jats:italic> missense variants were identified, with the most common variant being c.250G&gt;A (p.A84T), with an allelic frequency of 58.35 (7\/12).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jpem-2020-0689_abs_004\">\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p> These findings revealed that it is easy for patients with MADD to go unidentified, as they may have atypical acylcarnitine profiles at NBS and the recall stage, indicating the value of genetic analysis for confirming suspected inherited metabolic disorders in the NBS program. Therefore, false-negative (FN) results may be reduced by combining tandem mass spectrometry (MS\/MS) with genetic testing in NBS for MADD.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1515\/jpem-2020-0694","type":"journal-article","created":{"date-parts":[[2021,4,7]],"date-time":"2021-04-07T22:01:13Z","timestamp":1617832873000},"page":"649-652","source":"Crossref","is-referenced-by-count":9,"title":["Newborn screening and molecular features of patients with multiple acyl-CoA dehydrogenase deficiency in Quanzhou, China"],"prefix":"10.1515","volume":"34","author":[{"given":"Yiming","family":"Lin","sequence":"first","affiliation":[{"name":"Neonatal Disease Screening Center, Quanzhou Maternity and Children\u2019s Hospital , Quanzhou , Fujian Province , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weifeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neonatal Intensive Care Unit , Quanzhou Maternity and Children\u2019s Hospital , Quanzhou , Fujian Province , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhixu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Intensive Care Unit , Quanzhou Maternity and Children\u2019s Hospital , Quanzhou , Fujian Province , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunmei","family":"Lin","sequence":"additional","affiliation":[{"name":"Neonatal Disease Screening Center, Quanzhou Maternity and Children\u2019s Hospital , Quanzhou , Fujian Province , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weihua","family":"Lin","sequence":"additional","affiliation":[{"name":"Neonatal Disease Screening Center, Quanzhou Maternity and Children\u2019s Hospital , Quanzhou , Fujian Province , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingliu","family":"Fu","sequence":"additional","affiliation":[{"name":"Neonatal Disease Screening Center, Quanzhou Maternity and Children\u2019s Hospital , Quanzhou , Fujian Province , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weilin","family":"Peng","sequence":"additional","affiliation":[{"name":"Neonatal Disease Screening Center, Quanzhou Maternity and Children\u2019s Hospital , Quanzhou , Fujian Province , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongmei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neonatal Intensive Care Unit , Quanzhou Maternity and Children\u2019s Hospital , Quanzhou , Fujian Province , China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2021,4,7]]},"reference":[{"key":"2023040101405223239_j_jpem-2020-0694_ref_001","doi-asserted-by":"crossref","unstructured":"Yotsumoto, Y, Hasegawa, Y, Fukuda, S, Kobayashi, H, Endo, M, Fukao, T, et al.. Clinical and molecular investigations of Japanese cases of glutaric acidemia type 2. Mol Genet Metabol 2008;94:61\u20137. https:\/\/doi.org\/10.1016\/j.ymgme.2008.01.002.","DOI":"10.1016\/j.ymgme.2008.01.002"},{"key":"2023040101405223239_j_jpem-2020-0694_ref_002","doi-asserted-by":"crossref","unstructured":"Goodman, SI, Binard, RJ, Woontner, MR, Frerman, FE. Glutaric acidemia type II: gene structure and mutations of the electron transfer flavoprotein:ubiquinone oxidoreductase (ETF:QO) gene. Mol Genet Metabol 2002;77:86\u201390. https:\/\/doi.org\/10.1016\/s1096-7192(02)00138-5.","DOI":"10.1016\/S1096-7192(02)00138-5"},{"key":"2023040101405223239_j_jpem-2020-0694_ref_003","doi-asserted-by":"crossref","unstructured":"Olsen, RK, Andresen, BS, Christensen, E, Bross, P, Skovby, F, Gregersen, N. Clear relationship between ETF\/ETFDH genotype and phenotype in patients with multiple acyl-CoA dehydrogenation deficiency. Hum Mutat 2003;22:12\u201323. https:\/\/doi.org\/10.1002\/humu.10226.","DOI":"10.1002\/humu.10226"},{"key":"2023040101405223239_j_jpem-2020-0694_ref_004","doi-asserted-by":"crossref","unstructured":"van Rijt, WJ, Ferdinandusse, S, Giannopoulos, P, Ruiter, JPN, de Boer, L, Bosch, AM, et al.. Prediction of disease severity in Multiple acyl-CoA dehydrogenase deficiency: a retrospective and laboratory cohort study. J Inherit Metab Dis 2019;42:878\u201389. https:\/\/doi.org\/10.1002\/jimd.12147.","DOI":"10.1002\/jimd.12147"},{"key":"2023040101405223239_j_jpem-2020-0694_ref_005","doi-asserted-by":"crossref","unstructured":"Grunert, SC. Clinical and genetical heterogeneity of late-onset multiple acyl-coenzyme A dehydrogenase deficiency. Orphanet J Rare Dis 2014;9:117. https:\/\/doi.org\/10.1186\/s13023-014-0117-5.","DOI":"10.1186\/s13023-014-0117-5"},{"key":"2023040101405223239_j_jpem-2020-0694_ref_006","doi-asserted-by":"crossref","unstructured":"Olsen, RK, Olpin, SE, Andresen, BS, Miedzybrodzka, ZH, Pourfarzam, M, Merinero, B, et al.. ETFDH mutations as a major cause of riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency. Brain 2007;130:2045\u201354. https:\/\/doi.org\/10.1093\/brain\/awm135.","DOI":"10.1093\/brain\/awm135"},{"key":"2023040101405223239_j_jpem-2020-0694_ref_007","doi-asserted-by":"crossref","unstructured":"Liang, WC, Lin, YF, Liu, TY, Chang, SC, Chen, BH, Nishino, I, et al.. Neurite growth could be impaired by ETFDH mutation but restored by mitochondrial cofactors. Muscle Nerve 2017;56:479\u201385. https:\/\/doi.org\/10.1002\/mus.25501.","DOI":"10.1002\/mus.25501"},{"key":"2023040101405223239_j_jpem-2020-0694_ref_008","doi-asserted-by":"crossref","unstructured":"Goh, LL, Lee, Y, Tan, ES, Lim, JSC, Lim, CW, Dalan, R. Patient with Multiple acyl-CoA dehydrogenase deficiency disease and ETFDH mutations benefits from riboflavin therapy: a case report. BMC Med Genom 2018;11:37. https:\/\/doi.org\/10.1186\/s12920-018-0356-8.","DOI":"10.1186\/s12920-018-0356-8"},{"key":"2023040101405223239_j_jpem-2020-0694_ref_009","doi-asserted-by":"crossref","unstructured":"Van Rijt, WJ, Heiner-Fokkema, MR, du Marchie Sarvaas, GJ, Waterham, HR, Blokpoel, RG, van Spronsen, FJ, et al.. Favorable outcome after physiologic dose of sodium-D,L-3-hydroxybutyrate in severe MADD. 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J Mol Med (Berl) 2011;89:569\u201376. https:\/\/doi.org\/10.1007\/s00109-011-0725-7.","DOI":"10.1007\/s00109-011-0725-7"},{"key":"2023040101405223239_j_jpem-2020-0694_ref_014","doi-asserted-by":"crossref","unstructured":"Wen, B, Dai, T, Li, W, Zhao, Y, Liu, S, Zhang, C, et al.. Riboflavin-responsive lipid-storage myopathy caused by ETFDH gene mutations. J Neurol Neurosurg Psychiatry 2010;81:231\u20136. https:\/\/doi.org\/10.1136\/jnnp.2009.176404.","DOI":"10.1136\/jnnp.2009.176404"},{"key":"2023040101405223239_j_jpem-2020-0694_ref_015","doi-asserted-by":"crossref","unstructured":"Er, TK, Liang, WC, Chang, JG, Jong, YJ. High resolution melting analysis facilitates mutation screening of ETFDH gene: applications in riboflavin-responsive Multiple acyl-CoA dehydrogenase deficiency. Clin Chim Acta 2010;411:690\u20139. https:\/\/doi.org\/10.1016\/j.cca.2010.01.033.","DOI":"10.1016\/j.cca.2010.01.033"},{"key":"2023040101405223239_j_jpem-2020-0694_ref_016","doi-asserted-by":"crossref","unstructured":"Fan, X, Xie, B, Zou, J, Luo, J, Qin, Z, D\u2019Gama, AM, et al.. Novel ETFDH mutations in four cases of riboflavin responsive Multiple acyl-CoA dehydrogenase deficiency. Mol Gen Metab Rep 2018;16:15\u201319. https:\/\/doi.org\/10.1016\/j.ymgmr.2018.05.007.","DOI":"10.1016\/j.ymgmr.2018.05.007"},{"key":"2023040101405223239_j_jpem-2020-0694_ref_017","doi-asserted-by":"crossref","unstructured":"Zhu, M, Zhu, X, Qi, X, Weijiang, D, Yu, Y, Wan, H, et al.. Riboflavin-responsive multiple Acyl-CoA dehydrogenation deficiency in 13 cases, and a literature review in mainland Chinese patients. 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