Department of Pediatrics, Alberta Children's Hospital, 2888 Shaganappi Trail, NW, Calgary, AB, T3B 6A8, Canada.
Pediatr Nephrol. 2011 Aug;26(8):1335-7. doi: 10.1007/s00467-011-1904-z. Epub 2011 May 8.
Cystinosis is a rare autosomal recessive disease caused by mutations of the CTNS gene in which cystine accumulates throughout the body as a result of a defective efflux of cystine from lysosomes. Three phenotypic forms have been described according to the age of onset and the severity of the clinical symptoms: infantile, intermediate, and ocular non-nephropathic cystinosis. Here we report the natural history of cystinosis in a 55-year-old man with intermediate nephropathic cystinosis diagnosed at 9 years of age. Although tubulopathy was unnoticed in the early years, he required transplantation at age 16. Sequencing analysis of all the CTNS exons revealed that the proband is homozygous for a 21-bp in-frame deletion in exon 5 (c. 198_218del21), resulting in an in-frame deletion of 7 amino acids from the N-terminal domain of the cystinosin protein. Our patient has had relatively mild extra-renal disease despite lack of early cysteamine therapy. He has been able to attend university and pursue a professional career into the 6th decade.
胱氨酸贮积症是一种罕见的常染色体隐性遗传病，由 CTNS 基因突变引起，由于溶酶体中胱氨酸的排出功能缺陷，胱氨酸会在全身蓄积。根据发病年龄和临床症状的严重程度，可将其分为三种表型：婴儿型、中间型和眼-非肾病型胱氨酸贮积症。本研究报道了 1 例 9 岁时被诊断为中间型肾病型胱氨酸贮积症的 55 岁男性患者的自然病史。尽管在早期并未发现肾小管病变，但他在 16 岁时需要进行移植。对所有 CTNS 外显子进行测序分析显示，该先证者为第 5 外显子（c.198_218del21）21 个碱基对的框内缺失纯合子，导致胱氨酸蛋白酶 N 端结构域的 7 个氨基酸缺失。尽管未进行早期半胱氨酸治疗，我们的患者仍具有相对较轻的肾外疾病。他能够上大学，并在 60 多岁时继续从事专业职业。
