Scolamiero Emanuela, Cozzolino Carla, Albano Lucia, Ansalone Antonella, Caterino Marianna, Corbo Graziella, di Girolamo Maria Grazia, Di Stefano Cristina, Durante Adriano, Franzese Giovanni, Franzese Ignazio, Gallo Giovanna, Giliberti Paolo, Ingenito Laura, Ippolito Giovanni, Malamisura Basilio, Mazzeo Pietro, Norma Antonella, Ombrone Daniela, Parenti Giancarlo, Pellecchia Silvana, Pecce Rita, Pierucci Ippolito, Romanelli Roberta, Rossi Anna, Siano Massimo, Stoduto Teodoro, Villani Guglielmo R D, Andria Generoso, Salvatore Francesco, Frisso Giulia, Ruoppolo Margherita
CEINGE-Biotecnologie Avanzate scarl, Napoli, Italy.
Mol Biosyst. 2015 Jun;11(6):1525-35. doi: 10.1039/c4mb00729h.
Inborn errors of metabolism are genetic disorders due to impaired activity of enzymes, transporters, or cofactors resulting in accumulation of abnormal metabolites proximal to the metabolic block, lack of essential products or accumulation of by-products. Many of these disorders have serious clinical consequences for affected neonates, and an early diagnosis allows presymptomatic treatment which can prevent severe permanent sequelae and in some cases death. Expanded newborn screening for these diseases is a promising field of targeted metabolomics. Here we report the application, between 2007 and 2014, of this approach to the identification of newborns in southern Italy at risk of developing a potentially fatal disease. The analysis of amino acids and acylcarnitines in dried blood spots by tandem mass spectrometry revealed 24 affected newborns among 45,466 infants evaluated between 48 and 72 hours of life (overall incidence: 1 : 1894). Diagnoses of newborns with elevated metabolites were confirmed by gas chromatography-mass spectrometry, biochemical studies, and genetic analysis. Five infants were diagnosed with medium-chain acyl CoA dehydrogenase deficiency, 1 with methylmalonic acidemia with homocystinuria type CblC, 2 with isolated methylmalonic acidemia, 1 with propionic acidemia, 1 with isovaleric academia, 1 with isobutyryl-CoA dehydrogenase deficiency, 1 with beta ketothiolase deficiency, 1 with short branched chain amino acid deficiency, 1 with 3-methlycrotonyl-CoA carboxylase deficiency, 1 with formimino-transferase cyclodeaminase deficiency, and 1 with cystathionine-beta-synthase deficiency. Seven cases of maternal vitamin B12 deficiency and 1 case of maternal carnitine uptake deficiency were detected. This study supports the widespread application of metabolomic-based newborn screening for these genetic diseases.
先天性代谢缺陷是由于酶、转运蛋白或辅助因子活性受损导致的遗传性疾病，可致使代谢阻滞近端的异常代谢产物蓄积、必需产物缺乏或副产物蓄积。这些疾病中的许多对受影响的新生儿具有严重的临床后果，早期诊断可进行症状前治疗，从而预防严重的永久性后遗症，在某些情况下还可预防死亡。针对这些疾病开展的扩大新生儿筛查是靶向代谢组学的一个有前景的领域。在此，我们报告了在2007年至2014年期间，将这种方法应用于意大利南部识别有患潜在致命疾病风险的新生儿。通过串联质谱分析干血斑中的氨基酸和酰基肉碱，在45466名出生后48至72小时接受评估的婴儿中发现了24名受影响的新生儿（总体发病率：1∶1894）。代谢产物升高的新生儿诊断通过气相色谱 - 质谱、生化研究和基因分析得以证实。5名婴儿被诊断为中链酰基辅酶A脱氢酶缺乏症，1名患有伴有同型胱氨酸尿症的CblC型甲基丙二酸血症，2名患有孤立性甲基丙二酸血症，1名患有丙酸血症，1名患有异戊酸血症，1名患有异丁酰辅酶A脱氢酶缺乏症，1名患有β-酮硫解酶缺乏症，1名患有短支链氨基酸缺乏症，1名患有3-甲基巴豆酰辅酶A羧化酶缺乏症，1名患有亚胺甲基转移酶环化脱氨酶缺乏症，1名患有胱硫醚-β-合酶缺乏症。检测到7例母亲维生素B12缺乏症和1例母亲肉碱摄取缺乏症。这项研究支持基于代谢组学的新生儿筛查在这些遗传疾病中的广泛应用。
