Dello Strologo Luca, Pras Elon, Pontesilli Claudia, Beccia Ercole, Ricci-Barbini Vittorino, de Sanctis Luisa, Ponzone Alberto, Gallucci Michele, Bisceglia Luigi, Zelante Leopoldo, Jimenez-Vidal Maite, Font Mariona, Zorzano Antonio, Rousaud Ferran, Nunes Virginia, Gasparini Paolo, Palacín Manuel, Rizzoni Gianfranco
Division of Nephrology and Dialysis, Bambino Gesù Children's Hospital and Research Institute, Rome, Italy.
J Am Soc Nephrol. 2002 Oct;13(10):2547-53. doi: 10.1097/01.asn.0000029586.17680.e5.
Recent developments in the genetics and physiology of cystinuria do not support the traditional classification, which is based on the excretion of cystine and dibasic amino acids in obligate heterozygotes. Mutations of only two genes (SLC3A1 and SLC7A9), identified by the International Cystinuria Consortium (ICC), have been found to be responsible for all three types of the disease. The ICC set up a multinational database and collected genetic and clinical data from 224 patients affected by cystinuria, 125 with full genotype definition. Amino acid urinary excretion patterns of 189 heterozygotes with genetic definition and of 83 healthy controls were also included. All SLC3A1 carriers and 14% of SLC7A9 carriers showed a normal amino acid urinary pattern (i.e., type I phenotype). The rest of the SLC7A9 carriers showed phenotype non-I (type III, 80.5%; type II, 5.5%). This makes the traditional classification imprecise. A new classification is needed: type A, due to two mutations of SLC3A1 (rBAT) on chromosome 2 (45.2% in our database); type B, due to two mutations of SLC7A9 on chromosome 19 (53.2% in this series); and a possible third type, AB (1.6%), with one mutation on each of the above-mentioned genes. Clinical data show that cystinuria is more severe in males than in females. The two types of cystinuria (A and B) had a similar outcome in this retrospective study, but the effect of the treatment could not be analyzed. Stone events do not correlate with amino acid urinary excretion. Renal function was clearly impaired in 17% of the patients.
胱氨酸尿症在遗传学和生理学方面的最新进展并不支持基于纯合子杂合子中胱氨酸和二碱基氨基酸排泄情况的传统分类。国际胱氨酸尿症协会（ICC）已确定，只有两个基因（SLC3A1和SLC7A9）的突变与该疾病的所有三种类型有关。ICC建立了一个跨国数据库，并收集了224名受胱氨酸尿症影响患者的遗传和临床数据，其中125名患者有完整的基因型定义。还纳入了189名有遗传学定义的杂合子和83名健康对照者的氨基酸尿排泄模式。所有SLC3A1携带者和14%的SLC7A9携带者表现出正常的氨基酸尿模式（即I型表型）。其余的SLC7A9携带者表现出非I型表型（III型，80.5%；II型，5.5%）。这使得传统分类不够精确。需要一种新的分类：A型，由于2号染色体上SLC3A1（rBAT）的两个突变（在我们的数据库中占45.2%）；B型，由于19号染色体上SLC7A9的两个突变（在本系列中占53.2%）；以及可能的第三种类型AB型（1.6%），上述每个基因各有一个突变。临床数据表明，胱氨酸尿症在男性中比在女性中更严重。在这项回顾性研究中，两种类型的胱氨酸尿症（A和B）有相似的结果，但无法分析治疗效果。结石事件与氨基酸尿排泄无关。17%的患者肾功能明显受损。
