Faculdade de Ciências Médicas, Departamento de Medicina Interna, Universidade do Estado do Rio de Janeiro, Serviço de Endocrinologia, Rio de Janeiro, RJ, Brazil.
Programa de Pós Graduação em Fisiopatologia Clínica e Experimental (FISCLINEX), Faculdade de Ciências Médicas, Rio de Janeiro, RJ, Brazil.
Calcif Tissue Int. 2023 Apr;112(4):512-517. doi: 10.1007/s00223-022-01051-2. Epub 2023 Jan 19.
Although vitamin D deficiency resulting from insufficient sunlight exposure or inadequate dietary vitamin D intake is the most common cause of rickets, mutations in genes involved in vitamin D metabolism can cause genetic forms of rickets termed Vitamin D-Dependent Rickets (VDDR). In 2018, Roizen et al. described a new type of VDDR, named VDDR3, caused by a recurrent missense mutation in the CYP3A4 gene that leads to accelerated inactivation of vitamin D metabolites. Here, we describe the third case of VDDR3 due to the same CYP3A4 mutation in a 2-year-old boy with bone deformities associated with poor growth. As in the previously reported cases, this patient had no family history of rickets. Serial measurements of vitamin D metabolites after a single 150,000 IU dose of cholecalciferol demonstrated an accelerated inactivation of 25(OH)D and 1,25(OH)2D. Significant improvement in growth velocity and healing of bone deformities were achieved after a short period of treatment with 10.000 IU of cholecalciferol daily, showing the importance of early recognition and prompt precision therapy of this condition.
虽然由于阳光暴露不足或饮食中维生素 D 摄入不足导致的维生素 D 缺乏是佝偻病最常见的原因，但维生素 D 代谢相关基因的突变可导致遗传性佝偻病，称为维生素 D 依赖性佝偻病（VDDR）。2018 年，Roizen 等人描述了一种新型的 VDDR，称为 VDDR3，由 CYP3A4 基因中的复发性错义突变引起，导致维生素 D 代谢物的加速失活。在这里，我们描述了第三个 VDDR3 病例，该病例是由于 CYP3A4 基因突变引起的，患者为 2 岁男孩，伴有骨骼畸形和生长不良。与之前报道的病例一样，该患者无佝偻病家族史。单次给予 150,000 IU 胆钙化醇后，对维生素 D 代谢物进行连续测量，结果表明 25(OH)D 和 1,25(OH)2D 的失活加速。在每日给予 10,000 IU 胆钙化醇进行短期治疗后，生长速度和骨骼畸形愈合均得到显著改善，表明早期识别和及时进行精准治疗的重要性。
