PDF(Pubmed)
Abstract：
BACKGROUND: Hereditary vitamin D resistant rickets (HVDRR) is a rare autosomal recessive disorder marked by end-organ resistance of 1,25-dihydroxyvitamin D secondary to various mutations in the vitamin D receptor gene. The currently accepted treatment modality involves bypassing the affected receptors in the gut with high-dose intravenous calcium. In a few limited case reports, cinacalcet, a calcimimetic, has been used as an adjunctive therapy.
METHODS: Retrospective chart reviews were conducted to collect the clinical and biochemical data of 8 patients with HVDRR from 5 Saudi families. Four patients received only high-dose calcium, while the remaining 4 received adjuvant cinacalcet. Serum chemistry and PTH levels were measured before and during cinacalcet treatment. Gene sequencing was performed to identify the disease-causing mutation.
RESULTS: All 8 patients exhibited alopecia and secondary hyperparathyroidism. Other clinical and biochemical features of rickets were present to varying degrees. Genetic analysis revealed 3 distinct mutations: a ligand-binding domain mutation in 3 unrelated patients, a ligand-binding domain mutation in 2 sisters, and a missense DNA-binding domain mutation in 3 brothers. While the overall response to therapy was variable, none of the 4 patients who received adjunctive cinacalcet developed hypocalcaemia, and there was some initial promise in improving serum PTH levels.
CONCLUSIONS: This series provides new insight into the clinical and biochemical characteristics as well as treatment responses in Saudi children with HVDRR. The findings suggest that cinacalcet is a safe and potentially valuable adjuvant in this understudied population; however, further research is required to verify these results.
METHODS: Retrospective chart reviews were conducted to collect the clinical and biochemical data of 8 patients with HVDRR from 5 Saudi families. Four patients received only high-dose calcium, while the remaining 4 received adjuvant cinacalcet. Serum chemistry and PTH levels were measured before and during cinacalcet treatment. Gene sequencing was performed to identify the disease-causing mutation.
RESULTS: All 8 patients exhibited alopecia and secondary hyperparathyroidism. Other clinical and biochemical features of rickets were present to varying degrees. Genetic analysis revealed 3 distinct mutations: a ligand-binding domain mutation in 3 unrelated patients, a ligand-binding domain mutation in 2 sisters, and a missense DNA-binding domain mutation in 3 brothers. While the overall response to therapy was variable, none of the 4 patients who received adjunctive cinacalcet developed hypocalcaemia, and there was some initial promise in improving serum PTH levels.
CONCLUSIONS: This series provides new insight into the clinical and biochemical characteristics as well as treatment responses in Saudi children with HVDRR. The findings suggest that cinacalcet is a safe and potentially valuable adjuvant in this understudied population; however, further research is required to verify these results.
摘要：
背景：遗传性维生素D抗性病（HVDRR）是一种罕见的常染色体隐性遗传疾病，其特征是1,25-二羟维生素D的终末器官抗性继发于维生素D受体基因的各种突变。目前接受的治疗方式包括用大剂量静脉内钙绕过肠道中受影响的受体。在一些有限的病例报告中，Cinacalcet,拟钙剂,已被用作辅助疗法。
方法：进行回顾性图表回顾，以收集来自5个沙特家庭的8例HVDRR患者的临床和生化数据。四名患者仅接受高剂量钙，其余4人接受西那卡塞佐剂治疗。在西那卡塞治疗之前和期间测量血清化学和PTH水平。进行基因测序以鉴定致病突变。
结果：所有8例患者均表现为脱发和继发性甲状旁腺功能亢进。病的其他临床和生化特征均有不同程度的表现。遗传分析显示3个不同的突变：3个无关患者的配体结合域突变，2姐妹中的配体结合域突变，和三个兄弟的错义DNA结合域突变。虽然对治疗的总体反应是可变的，接受辅助西那卡塞治疗的4例患者均未出现低钙血症，在改善血清PTH水平方面有一些初步的希望。
结论：本系列为沙特HVDRR儿童的临床和生化特征以及治疗反应提供了新的见解。研究结果表明，西那卡塞在这个未被研究的人群中是一种安全且潜在有价值的佐剂；然而，需要进一步的研究来验证这些结果。
方法：进行回顾性图表回顾，以收集来自5个沙特家庭的8例HVDRR患者的临床和生化数据。四名患者仅接受高剂量钙，其余4人接受西那卡塞佐剂治疗。在西那卡塞治疗之前和期间测量血清化学和PTH水平。进行基因测序以鉴定致病突变。
结果：所有8例患者均表现为脱发和继发性甲状旁腺功能亢进。病的其他临床和生化特征均有不同程度的表现。遗传分析显示3个不同的突变：3个无关患者的配体结合域突变，2姐妹中的配体结合域突变，和三个兄弟的错义DNA结合域突变。虽然对治疗的总体反应是可变的，接受辅助西那卡塞治疗的4例患者均未出现低钙血症，在改善血清PTH水平方面有一些初步的希望。
结论：本系列为沙特HVDRR儿童的临床和生化特征以及治疗反应提供了新的见解。研究结果表明，西那卡塞在这个未被研究的人群中是一种安全且潜在有价值的佐剂；然而，需要进一步的研究来验证这些结果。
