Chiba Yasushi, Inoue Chiyoko N
Department of Pediatrics, Red Cross Sendai Hospital.
Department of Pediatrics, Tohoku Rosai Hospital.
Tohoku J Exp Med. 2019 Jan;247(1):35-40. doi: 10.1620/tjem.247.35.
Cyclosporine A is known to be effective in some genetic podocyte injury. However, the efficacy of cyclosporine A depends on the degree of histopathological findings, and the relationship between long-term use and renal prognosis remains unknown. Frasier syndrome is a rare genetic disorder caused by intronic mutations in WT1, and is characterized by progressive glomerulopathy, a 46,XY disorder of sex development, and an increased risk of gonadoblastoma. We report here a 16-year-old phenotypically female patient with Frasier syndrome. A renal biopsy at the age of seven years showed segmentally effaced podocyte foot processes with no evidence of glomerulosclerosis. Steroid-resistant proteinuria progressed to the nephrotic range at the age of 10 years, which responded to once-daily administration of cyclosporine A with low two-hour post-dose cyclosporine A (C2) levels; she then achieved stable partial remission in combination with renin-angiotensin system (RAS) blockade. At the age of 12 years, examinations for delayed puberty confirmed the diagnosis of Frasier syndrome. The second renal biopsy showed widespread foot process effacement and a minor lesion of segmental glomerulosclerosis without findings suggestive of cyclosporine A nephropathy. She maintained partial remission and normal renal function with the continuation of once-daily low-dose cyclosporine A. The C2 levels required for the remission were between 212 and 520 ng/ml. Cyclosporine A dosages sufficient for maintaining the C2 levels were 1.1-1.2 mg/kg per day. In conclusion, the long-lasting treatment of once-daily low-dose cyclosporine A with RAS inhibition was effective for induction and maintenance of partial remission in Frasier syndrome.
已知环孢素A对某些遗传性足细胞损伤有效。然而，环孢素A的疗效取决于组织病理学表现的程度，长期使用与肾脏预后之间的关系尚不清楚。弗雷泽综合征是一种由WT1基因内含子突变引起的罕见遗传疾病，其特征是进行性肾小球病、46，XY性发育障碍和性腺母细胞瘤风险增加。我们在此报告一名16岁表型为女性的弗雷泽综合征患者。7岁时进行的肾活检显示节段性足细胞足突消失，无肾小球硬化证据。10岁时，激素抵抗性蛋白尿进展至肾病范围，每日一次给予环孢素A且给药后两小时环孢素A（C2）水平较低时蛋白尿有所缓解；随后联合肾素-血管紧张素系统（RAS）阻断治疗实现了稳定的部分缓解。12岁时，青春期延迟检查确诊为弗雷泽综合征。第二次肾活检显示广泛的足突消失和节段性肾小球硬化的轻微病变，无环孢素A肾病的表现。继续每日一次低剂量环孢素A治疗，她维持了部分缓解和正常肾功能。缓解所需的C2水平在212至520 ng/ml之间。维持C2水平所需的环孢素A剂量为每日1.1 - 1.2 mg/kg。总之，每日一次低剂量环孢素A联合RAS抑制的长期治疗对弗雷泽综合征诱导和维持部分缓解有效。
