Southern Medical University, Guangzhou, 510515, China.
Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, 510623, China.
Metab Brain Dis. 2017 Dec;32(6):2063-2071. doi: 10.1007/s11011-017-0097-y. Epub 2017 Sep 5.
Hydroxysteroid (17β) dehydrogenase 10 (HSD10) and mitochondrial acetoacetyl-CoA thiolase (β-KT) are two adjacent enzymes for the degradation of isoleucine, thus HSD10 and β-KT deficiencies are confusing at an early stage because of nearly the same elevation of typical metabolites in urine, such as 2-methyl-3-hydroxybutyric acid (2M3HBA) and tiglylglycine (TG). In order to better understand the differences between these two disorders, we described the clinical and molecular characteristics of two HSD10 deficiency patients and four β-KT deficiency patients. β-KT deficiency patients had a much more favorable outcome than that of HSD10 deficiency patients, indicating that the multifunction of HSD10, especially neurosteroid metabolic activity, other than only enzymatic degradation of isoleucine, is involved in the pathogenesis of HSD10 deficiency. Two different mutations, a novel mutation p.Ile175Met and a reported mutation p.Arg226Gln, were detected in the HSD17B10 gene of HSD10 deficiency patients. Six different mutations, including four known mutations: p.Ala333Pro, p.Thr297Lys, c.83_84delAT, c.1006-1G > C, and two novel mutations: p.Thr277Pro and c.121-3C > G were identified in the ACAT1 gene of β-KT deficiency patients. In general, DNA diagnosis played an important role in distinguishing between these two disorders.
羟甾体 17β 脱氢酶 10（HSD10）和线粒体乙酰乙酰辅酶 A 硫解酶（β-KT）是两种用于降解异亮氨酸的相邻酶，因此 HSD10 和 β-KT 缺乏症在早期会因尿液中典型代谢物（如 2-甲基-3-羟基丁酸（2M3HBA）和丁羟甘氨酸（TG））的升高而难以区分。为了更好地理解这两种疾病之间的差异，我们描述了两位 HSD10 缺乏症患者和四位 β-KT 缺乏症患者的临床和分子特征。β-KT 缺乏症患者的预后明显优于 HSD10 缺乏症患者，这表明 HSD10 的多功能性，特别是神经甾体代谢活性，而不仅仅是异亮氨酸的酶降解，参与了 HSD10 缺乏症的发病机制。在 HSD10 缺乏症患者的 HSD17B10 基因中检测到两种不同的突变，一种是新的突变 p.Ile175Met，另一种是报道过的突变 p.Arg226Gln。在 β-KT 缺乏症患者的 ACAT1 基因中鉴定出六种不同的突变，包括四种已知的突变：p.Ala333Pro、p.Thr297Lys、c.83_84delAT、c.1006-1G > C 和两个新的突变：p.Thr277Pro 和 c.121-3C > G。总的来说，DNA 诊断在区分这两种疾病方面发挥了重要作用。
