Bartter Syndrome Type 1 Due to Novel SLC12A1 Mutations Associated With Pseudohypoparathyroidism Type II.
Bartter Syndrome Type 1 Due to Novel SLC12A1 Mutations Associated With Pseudohypoparathyroidism Type II.
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DOI：
10.1210/jcemcr/luad019
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发表时间：
2023-03
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Bartter综合征1型是由编码氯化钠钾共转运蛋白2 （NKCC2）的溶质载体家族12成员1 （SLC12A1）突变引起的。除了引起肾失盐小管病变外，SLC12A1突变已知可引起高钙尿引起的肾钙质沉着症，以及与异常钙磷稳态相关的生长失败。我们报告一名患有多尿、低钠血症、低钾血症和代谢性碱中毒的7岁日本女孩，其中发现了复合杂合的新型SLC12A1突变。1岁后，甲状旁腺激素（PTH）水平持续升高，血清钙水平逐渐下降，血清磷水平逐渐升高。为了证实疑似甲状肾上腺素耐药，分别在不使用布洛芬或使用布洛芬的6 ~ 8个月和6 ~ 10个月时进行Ellsworth Howard试验。在PTH（1-34）输注的两种情况下，尿腺苷3′，5′-环单磷酸排泄量均增加，提示ⅱ型假性甲状旁腺功能低下。然而，只有在布洛芬治疗期间，甲状旁腺激素才会引起几乎正常的磷化反应。因此，非甾体类抗炎药可提高生长速度，减轻高钙尿症，增加甲状旁腺激素刺激的尿磷排泄，但不明显影响肾功能。
Bartter syndrome type 1 is caused by mutations in the solute carrier family 12 member 1 (SLC12A1), encoding the sodium-potassium-chloride cotransporter-2 (NKCC2). In addition to causing renal salt-losing tubulopathy, SLC12A1 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 SLC12A1 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.