Departamento de Ciencias Clínicas, Universidad de Las Palmas de Gran Canaria, Spain.
J Pediatr Gastroenterol Nutr. 2012 Jan;54(1):48-54. doi: 10.1097/MPG.0b013e318230130c.
The aim of the study was to characterize a group of 11 pediatric patients, ages 3 to 13 years, affected by Wilson disease (WD) in the island of Gran Canaria, Spain.
Genetic, biochemical, and pathological features, together with their response to treatment and clinical evolution, have been analyzed for this group of patients.
Genetically, the group was rather homogeneous, with an extremely high prevalence of the L708P mutation (4 homozygotes and 5 heterozygotes). Despite being initially screened because of asymptomatic hypertransaminemia, all of the patients presented with some degree of liver damage that was never accompanied by any neurological manifestation. Hepatic damage was most severe in a compound heterozygote with a novel mutation, G1266W, affecting a motif in the ATP7B polypeptide that is greatly conserved in similar proteins among metazoans. Ceruloplasmin and copper serum levels, together with the determination of hepatic copper content, were found to be of great diagnostic value, whereas urine copper measurements were found to be much less conclusive. All of the patients responded well to treatment with D-penicillamine with no documented adverse reactions.
The patients in Gran Canaria constitute, overall, one of the largest groups of patients with WD with a high incidence of a single mutation, allowing us to define the early clinical symptoms and the evolution of the disease in patients carrying the ATP7B L708P mutant allele, and the study of WD in a genetically homogeneous background.
本研究旨在对西班牙大加那利岛的 11 名 3 至 13 岁的威尔逊病（WD）患儿进行特征分析。
对该组患者的遗传、生化和病理特征，以及他们对治疗的反应和临床转归进行了分析。
在遗传上，该组患者非常同质，L708P 突变的发生率极高（4 个纯合子和 5 个杂合子）。尽管所有患者最初因无症状性高转氨酶血症而被筛查，但均有不同程度的肝损伤，且从未伴有任何神经表现。一位复合杂合子患者的肝损伤最为严重，该患者携带一种新的突变 G1266W，影响到多细胞动物中类似蛋白的 ATP7B 多肽中的一个基序。铜蓝蛋白和血清铜水平，以及肝铜含量的测定，对诊断具有很大的价值，而尿铜测量的结论性较差。所有患者均对 D-青霉胺治疗反应良好，无不良反应记录。
总的来说，大加那利岛的患者构成了 WD 患者中最大的群体之一，其单一突变的发生率较高，使我们能够定义携带 ATP7B L708P 突变等位基因的患者的早期临床症状和疾病演变，并对遗传同质背景下的 WD 进行研究。
