HUMAN BIOCHEMICAL GENETICS

1.人类遗传学分会发现75名胱氨酸病患者 而且大多数都是用半胱胺或磷酸半胱胺治疗。在Pre- 对于移植患者，半胱胺治疗是维持肾功能和 帮助成长。在移植后患者中，长期的并发症 描述了胱氨酸的积累。这些疾病包括肌病、神经疾病 介入，严重吞咽困难。半胱胺滴眼液(0.5%) 溶解青少年儿童角膜半胱氨酸晶体，去除混浊 从年龄较大的孩子的眼睛里，缓解了畏光症状。 2.游离唾液酸的溶酶体外流受损已被证实为 婴儿游离唾液酸蓄积症(ISSD)的基本缺陷。ISSD 成纤维细胞还储存葡萄糖醛酸，这是由于细胞外排出的葡萄糖醛酸受损 溶酶体。 3.唾液酸尿症的基本缺陷已被证明是受损的 CMP唾液酸对UDP N-乙酰氨基葡萄糖的反馈抑制作用 2-差向异构酶。细胞内游离唾液酸水平可通过治疗降低 胞苷对成纤维细胞的影响。 4.人肾可过滤，但不能再吸收游离唾液酸。这是 通过研究具有不同过滤负荷的患者的游离 唾液酸。 5.孟克斯氏病和印度儿童的铜代谢受损 肝硬变细胞。一种具有铜结合活性的23kD蛋白质正在研究中 以正常的人类成纤维细胞为特征。组氨酸铜治疗慢性阻塞性肺疾病 孟克斯氏病正在按照临床方案进行研究。 6.用碳水化合物研究未知的溶酶体储存障碍 通过脉冲安培检测和脂类分析进行分析 采用高效液相色谱分离和VAREX分析。 7.溶酶体膜载体正在通过重组进行研究 蛋白脂质体将被用作功能运输的测试系统。

1.Seventy-five cystinosis patients are seen in the Human Genetics Branch and most are treated with cysteamine or phosphocysteamine. In pre- transplant patients, cysteamine therapy is maintaining renal function and assisting growth. In post-transplant patients, complications of long-term cystine accumulation are described. These include myopathy, neurological involvement, and severe swallowing difficulties. Cysteamine eyedrops (0.5%) dissolve corneal cystine crystals in young children and remove the haziness from the eyes of older children, with relief of photophobia. 2.Impaired lysosomal egress of free sialic acid has been demonstrated as the basic defect in Infantile Free Sialic Acid Storage Disease (ISSD). ISSD fibroblasts also store glucuronic acid due to impaired egress out of the lysosome. 3.The basic defect in sialuria has been demonstrated to be impaired feedback inhibition by CMP sialic acid of UDP N-acetylglucosamine 2-epimerase. Cytosolic free sialic acid levels can be reduced by treatment of the fibroblasts with cytidine. 4.The human kidney filters but does not reabsorb free sialic acid. This was demonstrated by studying patients with different filtered loads of free sialic acid. 5.Copper metabolism is impaired in Menkes' disease and Indian Childhood Cirrhosis cells. A 23 Kd protein with copper-binding activity is being characterized using normal human fibroblasts. Copper histidinate therapy of Menkes' disease is being pursued by a clinical protocol. 6.Unknown lysosomal storage disorders are investigated by carbohydrate analysis performed by pulsed ampermetric detection, and by lipid analysis performed by HPLC separation and Varex analysis. 7.Lysosomal membrane carriers are being investigated by reconstitution of proteoliposomes to be used as a test system for functional transport.