Human Biochemical Genetics

人类生物化学遗传学部分调查罕见和信息丰富的先天性代谢错误，包括Hermansky？普德拉克综合征，胱氨酸病和尿酸钠。1. 该科成员继续发现导致HPS的四种已知基因的突变，并寻找导致该疾病的新基因。在与其他科学家的合作中，他们帮助开发了一种检测血小板中血清素的方法，评估了血小板缺陷患者的凝血分析仪，并描绘了HPS合并肺纤维化患者的放射学特征。该科迄今已检查、照顾和调查了120名HPS患者。2. 该科的成员跟踪了大约60例胱氨酸病患者，其中一些在肾移植前，一些在肾移植后。他们对新患者进行突变分析，积累治疗方案的纵向数据，并检测胱氨酸病的早期和晚期并发症。在与国家眼科研究所的医生合作中，该科帮助描述了胱氨酸病的前段并发症，并使用吲哚菁绿血管成像技术观察了胱氨酸病的视网膜。对半胱胺滴眼液新配方的研究也由第三部分公布。由于缺乏均质酸1,2-双加氧酶，均质酸（酪氨酸降解的中间体）积累导致尿酸。症状包括中年开始的关节和心脏瓣膜恶化。我们目前已经从临床、生化和分子方面对60多名尿尿患者进行了检查和调查。我们已经确定了90%的基因突变导致患者尿酸尿，并描述了一个患有尿酸尿和糖尿病肾病的人，他的肾脏疾病加重了他的衰老。两名患有尿尿症的妇女服用了低剂量的尼替西酮，这是一种抑制均质酸产生酶的药物。虽然血浆酪氨酸水平急剧上升，但均质酸产量的降低为使用尼替西酮治疗尿尿症提供了原理证明。4. 该科还研究其他各种罕见的人体代谢紊乱。该科成员已经确定了导致伊拉克-犹太人和非伊拉克-犹太人患者III型3-甲基戊二酸尿症的基因和突变。他们描述了一名患有Griscelli综合征的患者，该患者的神经系统受到rab27a而不是预期的肌球蛋白5A基因突变的影响。在与其他研究者的合作中，他们报道了由于编码溶酶体唾液酸转运体的基因突变而导致溶酶体游离唾液酸储存的患者。分部依然是世界？诊断唾液尿和其他游离唾液酸代谢紊乱的转诊实验室。

The Section on Human Biochemical Genetics investigates rare and informative inborn errors of metabolism, including Hermansky?Pudlak syndrome, cystinosis, and alkaptonuria. 1. Members of the Section continue to discover mutations in the four known genes causing HPS, and to search for new genes responsible for the disease. In collaboration with other scientists, they have helped develop an assay for detecting serotonin in platelets, evaluated a clotting analyzer for humans with platelet defects, and delineated the radiographic features of HPS patients with pulmonary fibrosis. The Section has examined, cared for,and investigated 120 HPS patients to date. 2. Members of the Section follow approximately 60 patients with cystinosis, some before and some after renal transplantation. They perform mutation analysis on patients new to the protocol, accumulate longitudinal data on treatment regimens, and detect early and late complications of cystinosis. In collaboration with physicians in the National Eye Institute, the Section has helped to describe anterior segment complications of cystinosis and retinal visualization in cystinosis using indocyanine green videoangiography. A study of a new formulation of cysteamine eyedrops was also promulgated by the Section. 3. Alkaptonuria results from accumulation of homogentisic acid, an intermediate in tyrosine degradation, due to deficiency of homogentisate 1,2-dioxygenase. The symptoms include joint and cardiac valve deterioration beginning in mid-life. We have now examined and investigated more than 60 alkaptonuria patients on clinical, biochemical, and molecular grounds. We have identified 90% of the genetic mutations causing alkaptonuria in our patients, and have described a man with alkaptonuria and diabetic nephropathy whose renal disease exacerbated his ochronosis. Two women with alkaptonuria were given low doses of nitisinone, a drug which inhibits the enzyme producing homogentisic acid. Although plasma tyrosine levels rose dramatically, the lowering of homogentisic acid production provides proof of principle for the use of nitisinone in alkaptonuria. 4. The Section also pursues a variety of other rare disorders of human metabolism. Members of the Section have identified the gene and the mutations responsible for type III 3-methylglutaconic aciduria in Iraqi-Jewish and non-Iraqi-Jewish patients. They have described a patient with Griscelli syndrome and neurological involvement caused by mutations in rab27a rather than the expected gene, myosin 5A. In collaboration with other investigators, they have reported patients with lysosomal free sialic acid storage due to mutations in the gene encoding the lysosomal sialic acid transporter. The Section remains the world?s referral laboratory for diagnosing sialuria and other disorders of free sialic acid metabolism.