Human Biochemical Genetics

人类生物化学遗传学部分研究选择的先天性代谢错误，以提供对细胞机制的洞察和对被遗弃患者群体的护理。1. Hermansky-Pudlak综合征（HPS）是一种罕见的眼部皮肤白化病和出血疾病，由黑素体和血小板致密体的异常形成引起。这种疾病有7种遗传亚型。该组成员描述了6例新的非波多黎各HPS-1患者，伴有4例新的HPS1突变，以及7例新的非波多黎各HPS-4患者，伴有3例新的HPS4突变。我们继续定义HPS亚型临床参与的自然历史，并对这些疾病中细胞内囊泡的运动进行细胞生物学研究。2. 今年，该科的成员在临床中心接收了70多名胱氨酸病患者，他们接受了半胱胺治疗，并记录了该疾病的非肾脏并发症的存在或不存在。一名25岁男子患有冠状动脉疾病，现在被报道为胱氨酸病的晚期并发症。一名患有眼胱氨酸病的妇女被诊断为多发性骨髓瘤。据报道，两名接受半胱胺治疗的兄弟姐妹在14岁和8岁时具有良好的肾功能和生长。该科成员与国家眼科研究所合作，继续研究治疗角膜胱氨酸晶体的半胱胺滴眼液。3. 该科扩大了其在尿酸症方面的专业知识，尿酸症是由于缺乏均质酸1,2-双加氧酶而导致的均质酸积累紊乱。本节记录了该疾病在关节、肾结石和心脏瓣膜方面的自然病史，并开始使用尼替西酮治疗5例患者，尼替西酮使毒性均质酸减少95%。突变分析也在分组的患者中进行。年代的研究。4. 该科成员诊断并描述了三种不同的游离唾液酸代谢紊乱患者，即Salla病和婴儿游离唾液酸储存病。这些疾病是由唾液素缺陷引起的，唾液素是溶酶体膜运输蛋白，它将游离唾液酸从溶酶体中携带出来。5. 该科还研究了选定的罕见病患者，包括2例灰色血小板综合征和3例遗传性包涵体肌病。后一种疾病的缺陷酶，UDP-GlcNAc 2- epimase，在培养成纤维细胞中检测。同时对患者进行突变分析。DNA。研究方案旨在寻找灰色血小板综合征的基因，并记录常染色体隐性多囊肾病和先天性肝纤维化的自然病史。

The Section on Human Biochemical Genetics studies selected inborn errors of metabolism to provide insight into cellular mechanisms and care for abandoned populations of patients. 1. Hermansky-Pudlak syndrome (HPS) is a rare disorder of oculocutaneous albinism and bleeding due to abnormal formation of melanosomes and platelet dense bodies. There are 7 genetic subtypes of this disease. Members of the Section described 6 new, non-Puerto Rican HPS-1 patients along with 4 novel HPS1 mutations, and 7 new, non-Puerto Rican HPS-4 patients having 3 novel HPS4 mutations. We continue to define the natural history of clinical involvement in the subtypes of HPS, and to perform cell biological studies of the movement of intracellular vesicles in these disorders. 2. This year members of the Section admitted more than 70 cystinosis patients to the Clinical Center, following their treatment with cysteamine and documenting the presence or absence of nonrenal complications of the disorder. One 25-year old man had coronary artery disease, and this is now being reported as a late complication of cystinosis. One woman carrying the diagnosis of ocular cystinosis was diagnosed instead with multiple myeloma. Two siblings treated well with cysteamine were reported to have excellent kidney function and growth at ages 14 and 8. In collaboration with the National Eye Institute, members of the Section continue to investigate cysteamine eyedrops for the treatment of corneal cystine crystals. 3. The Section has expanded its expertise in alkaptonuria, a disorder of accumulation of homogentisic acid due to deficiency of homogentisate 1,2-dioxygenase. The Section documented the natural history of the disease with respect to joints, kidney stones, and cardiac valves, and began therapy in 5 patients with nitisinone, which reduced the toxic homogentisic acid by 95%. Mutation analysis was also performed in patients enrolled in the Section?s studies. 4. Members of the Section diagnosed and described three different patients with disorders of free sialic acid metabolism, i.e., Salla disease and Infantile Free Sialic Acid Storage Disease. These disorders results from defective sialin, the lysosomal membrane transport protein which carries free sialic acid out of lysosomes. 5. The Section also studied selected rare disease patients, including two with Gray Platelet Syndrome and three with Hereditary Inclusion Body Myopathy. The deficient enzyme in this latter disease, UDP-GlcNAc 2-epimerase, was assayed in cultured fibroblasts. Mutation analysis was also performed on the patients? DNA. Protocols were initiated to find the gene causing Gray Platelet Syndrome and to document the natural history of Autosomal Recessive Polycystic Kidney Disease and Congenital Hepatic Fibrosis.