Department of Pediatrics, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
J Clin Endocrinol Metab. 2013 Dec;98(12):E2022-7. doi: 10.1210/jc.2013-2571. Epub 2013 Sep 30.
Although AP2S1 has recently been shown to be a causative gene for familial hypocalciuric hypercalcemia type 3 (FHH3), knowledge about FHH3 remains poor.
Our objective was to report AP2S1 mutation and effects of low calcium formula in a patient with hypercalcemia and hypercalciuria.
This Japanese female infant was found to have hypercalcemia by a routine laboratory test for poor weight gain on breast feeding. At 49 days of age, serum calcium (adjusted by Payne's formula) was 13.1 mg/dL, intact PTH 27 pg/mL, and urinary calcium-to-creatinine ratio 1.29 mg/mg. There was no evidence for hyperparathyroidism, PTHrP-producing neoplasm, and vitamin D excess. These data, except for hypercalciuria, appeared to be consistent with defective calcium-sensing receptor-mediated signaling. With use of low calcium formula containing 2.6 mg/dL of calcium, she showed catch-up growth, and serum calcium was decreased, as was urinary calcium-to-creatinine ratio. Furthermore, feeding with a mixture of low calcium formula and standard formula with a 2:1 ratio maintained serum calcium ∼12 mg/dL without markedly increasing serum PTH.
Although no pathologic mutation was detected in CASR or GNA11, a presumably de novo heterozygous mutation (p.Arg15Leu), a previously reported causative mutation for FHH3, was identified in AP2S1 of this patient.
The results imply that lack of hypocalciuria does not necessarily argue against the presence of AP2S1 mutations. The early infantile age of this patient would have played a certain role in the occurrence of hypercalciuria, and low calcium formula is worth attempting in infants with FHH.
尽管 AP2S1 最近被证实是家族性低钙性高钙血症 3 型（FHH3）的致病基因，但人们对 FHH3 的认识仍然有限。
我们旨在报告 1 例高钙血症和高钙尿症患者的 AP2S1 突变和低钙配方的影响。
这名日本女婴因母乳喂养体重增长不佳而在常规实验室检查中发现高钙血症。49 天时，血清钙（按 Payne 公式校正）为 13.1mg/dL，完整 PTH 为 27pg/mL，尿钙/肌酐比值为 1.29mg/mg。无甲状旁腺功能亢进、PTHrP 分泌肿瘤和维生素 D 过多的证据。除高钙尿症外，这些数据似乎与钙敏感受体介导的信号转导缺陷一致。使用含有 2.6mg/dL 钙的低钙配方，她的生长速度加快，血清钙和尿钙/肌酐比值均降低。此外，以低钙配方和标准配方 2:1 的比例混合喂养可使血清钙维持在 12mg/dL 左右，而不会显著增加血清 PTH。
尽管在 CASR 或 GNA11 中未检测到病理性突变，但在该患者的 AP2S1 中发现了一个假定的从头杂合突变（p.Arg15Leu），这是之前报道的 FHH3 的致病突变。
这些结果表明，缺乏低钙尿症并不一定排除 AP2S1 突变的存在。该患者的婴儿早期年龄在高钙尿症的发生中起到了一定的作用，低钙配方在 FHH 婴儿中值得尝试。
