Schlune Andrea, Riederer Anselma, Mayatepek Ertan, Ensenauer Regina
Experimental Pediatrics and Metabolism, Department of General Pediatrics, Neonatology and Pediatric Cardiology, Heinrich Heine University Düsseldorf, Moorenstrasse 5, 40225 Düsseldorf, Germany.
Department of Obstetrics and Gynecology, Hospital Altötting-Burghausen, Teaching Hospital of the Ludwig-Maximilians-Universität München, Vinzenz-von-Paul-Strasse 10, 84503 Altötting, Germany.
Int J Neonatal Screen. 2018 Jan 29;4(1):7. doi: 10.3390/ijns4010007. eCollection 2018 Mar.
Isovaleric acidemia (IVA), an inborn error of leucine catabolism, is caused by mutations in the isovaleryl-CoA dehydrogenase () gene, resulting in the accumulation of derivatives of isovaleryl-CoA including isovaleryl (C5)-carnitine, the marker metabolite used for newborn screening (NBS). The inclusion of IVA in NBS programs in many countries has broadened knowledge of the variability of the condition, whereas prior to NBS, two distinct clinical phenotypes were known, an "acute neonatal" and a "chronic intermittent" form. An additional biochemically mild and potentially asymptomatic form of IVA and its association with a common missense mutation, c.932C>T (p.A282V), was discovered in subjects identified through NBS. Deficiency of short/branched chain specific acyl-CoA dehydrogenase (2-methylbutyryl-CoA dehydrogenase), a defect of isoleucine degradation whose clinical significance remains unclear, also results in elevated C5-carnitine, and may therefore be detected by NBS for IVA. Treatment strategies for the long-term management of symptomatic IVA comprise the prevention of catabolism, dietary restriction of natural protein or leucine intake, and supplementation with l-carnitine and/or l-glycine. Recommendations on how to counsel and manage individuals with the mild phenotype detected by NBS are required.
异戊酸血症（IVA）是一种亮氨酸分解代谢的先天性疾病，由异戊酰辅酶A脱氢酶（）基因突变引起，导致包括异戊酰（C5）-肉碱在内的异戊酰辅酶A衍生物积累，异戊酰（C5）-肉碱是用于新生儿筛查（NBS）的标志物代谢物。许多国家将IVA纳入NBS项目，拓宽了对该病变异性的认识，而在NBS之前，已知两种不同的临床表型，即“急性新生儿型”和“慢性间歇性型”。通过NBS识别出的受试者中发现了一种生化表现较轻且可能无症状的IVA形式及其与常见错义突变c.932C>T（p.A282V）的关联。短/支链特异性酰基辅酶A脱氢酶（2-甲基丁酰辅酶A脱氢酶）缺乏，这是一种异亮氨酸降解缺陷，其临床意义尚不清楚，也会导致C5-肉碱升高，因此可能通过IVA的NBS检测出来。有症状IVA长期管理的治疗策略包括预防分解代谢、限制天然蛋白质或亮氨酸摄入的饮食、补充左旋肉碱和/或左旋甘氨酸。需要有关如何咨询和管理通过NBS检测出的轻度表型个体的建议。
