PDF(Pubmed)
Abstract：
UNASSIGNED: 24-Hydroxylase, encoded by the CYP24A1 gene, is a crucial enzyme involved in the catabolism of vitamin D. Loss-of-function mutations in CYP24A1 result in PTH-independent hypercalcaemia with high levels of 1,25(OH)2D3. The variety of clinical manifestations depends on age, and underlying genetic predisposition mutations can lead to fatal infantile hypercalcaemia among neonates, whereas adult symptoms are usually mild.
UNASSIGNED: We report a rare case of an adult with primary hyperparathyroidism and loss-of-function mutations in the CYP24A1 gene and a review of similar cases.
UNASSIGNED: We report the case of a 58-year-old woman diagnosed initially with primary hyperparathyroidism. Preoperatively, the suspected mass adjoining the upper pole of the left lobe of the thyroid gland was found via ultrasonography and confirmed by 99mTc scintigraphy and biopsy as the parathyroid gland. The patient underwent parathyroidectomy (a histopathology report revealed parathyroid adenoma), which led to normocalcaemia. After 10 months, vitamin D supplementation was introduced due to deficiency, and the calcium level remained within the reference range. Two years later, biochemical tests showed recurrence of hypercalcaemia with suppressed parathyroid hormone levels and elevated 1,25(OH)2D3 concentrations. Further investigation excluded the most common causes of PTH-independent hypercalcaemia, such as granulomatous disease, malignancy, and vitamin D intoxication. Subsequently, vitamin D metabolites were measured using LC-MS/MS, which revealed high levels of 25(OH)D3, low levels of 24,25(OH)2D3 and elevated 25(OH)2D3/24,25(OH)2D3 ratios, suggesting a defect in vitamin D catabolism. Molecular analysis of the CYP24A1 gene using the NGS technique revealed two pathogenic variants: p.(Arg396Trp) and p.(Glu143del) (rs114368325 and rs777676129, respectively).
UNASSIGNED: The diagnostic process for hypercalcaemia becomes complicated when multiple causes of hypercalcaemia coexist. The measurement of vitamin D metabolites using LC-MS/MS may help to identify carriers of CYP24A1 mutations. Subsequent molecular testing may contribute to establishing the exact frequency of pathogenic variants of the CYP24A1 gene and introducing personalized treatment.
UNASSIGNED: We report a rare case of an adult with primary hyperparathyroidism and loss-of-function mutations in the CYP24A1 gene and a review of similar cases.
UNASSIGNED: We report the case of a 58-year-old woman diagnosed initially with primary hyperparathyroidism. Preoperatively, the suspected mass adjoining the upper pole of the left lobe of the thyroid gland was found via ultrasonography and confirmed by 99mTc scintigraphy and biopsy as the parathyroid gland. The patient underwent parathyroidectomy (a histopathology report revealed parathyroid adenoma), which led to normocalcaemia. After 10 months, vitamin D supplementation was introduced due to deficiency, and the calcium level remained within the reference range. Two years later, biochemical tests showed recurrence of hypercalcaemia with suppressed parathyroid hormone levels and elevated 1,25(OH)2D3 concentrations. Further investigation excluded the most common causes of PTH-independent hypercalcaemia, such as granulomatous disease, malignancy, and vitamin D intoxication. Subsequently, vitamin D metabolites were measured using LC-MS/MS, which revealed high levels of 25(OH)D3, low levels of 24,25(OH)2D3 and elevated 25(OH)2D3/24,25(OH)2D3 ratios, suggesting a defect in vitamin D catabolism. Molecular analysis of the CYP24A1 gene using the NGS technique revealed two pathogenic variants: p.(Arg396Trp) and p.(Glu143del) (rs114368325 and rs777676129, respectively).
UNASSIGNED: The diagnostic process for hypercalcaemia becomes complicated when multiple causes of hypercalcaemia coexist. The measurement of vitamin D metabolites using LC-MS/MS may help to identify carriers of CYP24A1 mutations. Subsequent molecular testing may contribute to establishing the exact frequency of pathogenic variants of the CYP24A1 gene and introducing personalized treatment.
摘要：
■24-羟化酶，由CYP24A1基因编码，是参与维生素D分解代谢的关键酶。CYP24A1中的功能丧失突变导致PTH非依赖性高钙血症，并具有高水平的1,25（OH）2D3。临床表现的多样性取决于年龄，潜在的遗传易感性突变会导致新生儿致命的婴儿高钙血症，而成人症状通常是轻微的。
■我们报告了一例罕见的成人原发性甲状旁腺功能亢进和CYP24A1基因功能丧失突变病例，并对类似病例进行了回顾。
■我们报告了一例58岁女性，最初诊断为原发性甲状旁腺功能亢进。术前,通过超声检查发现了与甲状腺左叶上极相邻的可疑肿块，并通过99mTc闪烁显像和活检证实为甲状旁腺。患者接受了甲状旁腺切除术（组织病理学报告显示甲状旁腺腺瘤），导致了正常钙血症.10个月后,维生素D补充剂是由于缺乏而引入的，钙水平保持在参考范围内。两年后,生化检查显示高钙血症复发,甲状旁腺激素水平降低,1,25(OH)2D3浓度升高.进一步的调查排除了PTH非依赖性高钙血症的最常见原因，如肉芽肿病，恶性肿瘤，和维生素D中毒。随后，使用LC-MS/MS测量维生素D代谢物，这表明高水平的25(OH)D3，低水平的24,25(OH)2D3和升高的25(OH)2D3/24,25(OH)2D3比率，提示维生素D分解代谢缺陷.使用NGS技术对CYP24A1基因进行的分子分析揭示了两种致病变体：p。（Arg396Trp）和p。（Glu143del）（分别为rs114368325和rs777676129）。
■当多种原因共存时，高钙血症的诊断过程变得复杂。使用LC-MS/MS测量维生素D代谢物可能有助于鉴定CYP24A1突变的携带者。随后的分子检测可能有助于确定CYP24A1基因致病变异的确切频率并引入个性化治疗。
■我们报告了一例罕见的成人原发性甲状旁腺功能亢进和CYP24A1基因功能丧失突变病例，并对类似病例进行了回顾。
■我们报告了一例58岁女性，最初诊断为原发性甲状旁腺功能亢进。术前,通过超声检查发现了与甲状腺左叶上极相邻的可疑肿块，并通过99mTc闪烁显像和活检证实为甲状旁腺。患者接受了甲状旁腺切除术（组织病理学报告显示甲状旁腺腺瘤），导致了正常钙血症.10个月后,维生素D补充剂是由于缺乏而引入的，钙水平保持在参考范围内。两年后,生化检查显示高钙血症复发,甲状旁腺激素水平降低,1,25(OH)2D3浓度升高.进一步的调查排除了PTH非依赖性高钙血症的最常见原因，如肉芽肿病，恶性肿瘤，和维生素D中毒。随后，使用LC-MS/MS测量维生素D代谢物，这表明高水平的25(OH)D3，低水平的24,25(OH)2D3和升高的25(OH)2D3/24,25(OH)2D3比率，提示维生素D分解代谢缺陷.使用NGS技术对CYP24A1基因进行的分子分析揭示了两种致病变体：p。（Arg396Trp）和p。（Glu143del）（分别为rs114368325和rs777676129）。
■当多种原因共存时，高钙血症的诊断过程变得复杂。使用LC-MS/MS测量维生素D代谢物可能有助于鉴定CYP24A1突变的携带者。随后的分子检测可能有助于确定CYP24A1基因致病变异的确切频率并引入个性化治疗。
