Loyer Camille, Leroy Clara, Molin Arnaud, Odou Marie-Françoise, Huglo Damien, Lion Georges, Ernst Olivier, Hoffmann Maxime, Porchet Nicole, Carnaille Bruno, Pattou François, Kottler Marie-Laure, Vantyghem Marie-Christine
Endocrinology and Metabolism Department, C. Huriez Hospital, Lille University Hospital, 1, rue Polonovski, 59037 Lille cedex, France.
Department of Genetics, University Hospital, 14000 Caen, France.
Ann Endocrinol (Paris). 2016 Oct;77(5):615-619. doi: 10.1016/j.ando.2016.03.002. Epub 2016 Jul 1.
CYP24A1 gene mutations induce infantile hypercalcemia, with high 1,25(OH)D contrasting with low PTH levels. The adult phenotype is not well known. Two unrelated adult patients were referred for nephrolithiasis, hypertension, hypercalcemia, hypercalciuria, normal 25-OHD levels, and inappropriate PTH levels (22 to 92pg/mL;N: 15-68) suggesting primary hyperparathyroidism, leading to surgery. Hypercalciuria improved despite persistent hypercalcemia, treated with cinacalcet. The ratio 25-OHD/24-25-(OH)2D>100 (N<25) suggested the diagnosis of CYP24A1 mutations which were confirmed through Sanger sequencing. In conclusion, the adult phenotype associated with CYP24A1 mutations can evolve over time from hypercalcemia with suppressed PTH towards hyperparathyroidism with moderately increased PTH level, adenoma and/or slightly increased parathyroid glands. Surgery decreased calciuria and improved kidney function. Cinacalcet was partially effective on hypercalcemia since PTH was inappropriate. This novel phenotype, a phenocopy of hyperparathyroidism, might evolve in few cases towards hyperparathyroidism despite random association of the 2 diseases cannot be excluded.
CYP24A1基因突变可导致婴儿高钙血症，其1,25(OH)D水平升高，而甲状旁腺激素（PTH）水平降低。成人的表型尚不清楚。两名无亲缘关系的成年患者因肾结石、高血压、高钙血症、高钙尿症、25-OHD水平正常以及PTH水平异常（22至92pg/mL；正常范围：15 - 68）而就诊，提示原发性甲状旁腺功能亢进，随后接受了手术治疗。尽管高钙血症持续存在，但使用西那卡塞治疗后高钙尿症有所改善。25-OHD/24 - 25-(OH)2D比值>100（正常范围<25）提示CYP24A1基因突变，通过桑格测序得以证实。总之，与CYP24A1基因突变相关的成人表型可能会随时间从PTH受抑制的高钙血症演变为PTH水平中度升高、伴有腺瘤和/或甲状旁腺轻度增大的甲状旁腺功能亢进。手术降低了尿钙水平并改善了肾功能。由于PTH水平异常，西那卡塞对高钙血症仅部分有效。这种新的表型，即甲状旁腺功能亢进的拟表型，在少数情况下可能会演变为甲状旁腺功能亢进，尽管不能排除这两种疾病的偶然关联。
