Kiuchi Zentaro, Nozu Kandai, Yan Kunimasa, Jüppner Harald
Department of Pediatrics, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
JCEM Case Rep. 2023 Feb 24;1(2):luad019. doi: 10.1210/jcemcr/luad019. eCollection 2023 Mar.
Bartter syndrome type 1 is caused by mutations in the solute carrier family 12 member 1 (), encoding the sodium-potassium-chloride cotransporter-2 (NKCC2). In addition to causing renal salt-losing tubulopathy, mutations are known to cause nephrocalcinosis due to hypercalciuria, as well as failure to thrive associated with abnormal calcium and phosphorus homeostasis. We report a now 7-year-old Japanese girl with polyuria, hyponatremia, hypokalemia, and metabolic alkalosis, in whom compound heterozygous novel mutations were identified. Elevated parathyroid hormone (PTH) levels were consistently noted after the age of 1 year in conjunction with gradually declining serum calcium and increasing serum phosphorus levels. To confirm suspected PTH-resistance, Ellsworth Howard tests were performed at the ages of 6 years 8 months and 6 years 10 months in the absence or presence of ibuprofen, respectively. Urinary adenosine 3',5'-cyclic monophosphate excretion increased on both occasions in response to PTH(1-34) infusion suggesting pseudohypoparathyroidism type II. However, only during treatment with ibuprofen did PTH induce an almost normal phosphaturic response. The nonsteroidal anti-inflammatory drugs thus enhanced growth velocity, alleviated hypercalciuria, and increased PTH-stimulated urinary phosphorus excretion without significantly affecting renal function.
1型巴特综合征由溶质载体家族12成员1（）的突变引起，该基因编码钠-钾-氯共转运蛋白-2（NKCC2）。除了导致肾失盐性肾小管病外，已知该突变还会因高钙尿症导致肾钙质沉着症，以及因钙和磷稳态异常导致生长发育迟缓。我们报告了一名现年7岁的日本女孩，她有多尿、低钠血症、低钾血症和代谢性碱中毒，在其身上发现了复合杂合的新型突变。1岁以后，甲状旁腺激素（PTH）水平持续升高，同时血清钙逐渐下降，血清磷升高。为了证实疑似的PTH抵抗，分别在6岁8个月和6岁10个月时，在不存在或存在布洛芬的情况下进行了埃尔斯沃思·霍华德试验。在输注PTH（1-34）时，两次尿中3'，5'-环磷酸腺苷排泄均增加，提示II型假性甲状旁腺功能减退。然而，只有在使用布洛芬治疗期间，PTH才诱导出几乎正常的磷尿反应。因此，非甾体抗炎药提高了生长速度，减轻了高钙尿症，并增加了PTH刺激的尿磷排泄，而对肾功能没有显著影响。
