Department of Endocrinology, Seth G.S Medical College and KEM Hospital, Mumbai, Maharashtra, India.
Department of Endocrinology, Vydehi institute of medical sciences and research centre, Bangalore, Karnataka, India.
J Pediatr Endocrinol Metab. 2021 Sep 8;34(12):1505-1513. doi: 10.1515/jpem-2021-0403. Print 2021 Dec 20.
Vitamin D dependent rickets type 1 (VDDR1) is a rare disease due to pathogenic variants in 1- hydroxylase gene. We describe our experience with systematic review of world literature to describe phenotype and genotype.
Seven patients from six unrelated families with genetically proven VDDR1 from our cohort and 165 probands from systematic review were analyzed retrospectively. The clinical features, biochemistry, genetics, management, and long-term outcome were retrieved.
In our cohort, the median age at presentation and diagnosis was 11(4-18) and 40(30-240) months. The delayed diagnoses were due to misdiagnoses as renal tubular acidosis and hypophosphatemic rickets. Four had hypocalcemic seizures in infancy whereas all had rickets by 2 years. All patients had biochemical response to calcitriol, however two patients diagnosed post-puberty had persistent deformity. Genetic analysis revealed two novel (p.Met260Arg, p.Arg453Leu) and a recurring variant (p.Phe443Profs*24). Systematic review showed that seizures as most common presentation in infancy, whereas delayed motor milestones and deformities after infancy. Diagnosis was delayed in 27 patients. Patients with unsatisfactory response despite compliance were >12 years at treatment initiation. Inappropriately normal 1,25(OH)2D may be present, however suppressed ratio of 1,25(OH)2 D/25(OH)D may provide a clue to diagnosis. Various region specific and hot-spot recurrent variants are described. Patients with truncating variants had higher daily calcitriol requirement and greatly suppressed ratio of 1,25(OH)2D/25(OH)D.
Delayed diagnosis may lead to permanent short stature and deformities. Truncating variants tend to have severe disease as compared to non-truncating variants. Diagnostic accuracy of 1,25(OH)2 D/25(OH)D ratio needs further validation.
维生素 D 依赖性佝偻病 1 型（VDDR1）是一种罕见疾病，由 1-羟化酶基因突变引起。我们通过系统综述世界文献来描述表型和基因型，介绍我们的经验。
从我们的队列中，有 7 名遗传性 VDDR1 的患者来自 6 个无关的家庭，以及从系统综述中选取 165 名先证者进行回顾性分析。我们检索了临床特征、生物化学、遗传学、管理和长期预后。
在我们的队列中，就诊和诊断时的中位年龄为 11（4-18）和 40（30-240）个月。由于误诊为肾小管性酸中毒和低磷性佝偻病，导致诊断延迟。4 名婴儿期有低钙性抽搐，而所有患儿在 2 岁时都有佝偻病。所有患者对骨化三醇均有生化反应，但 2 名青春期后诊断的患者仍有持续性畸形。基因分析显示有 2 个新的（p.Met260Arg，p.Arg453Leu）和一个反复出现的变异（p.Phe443Profs*24）。系统综述显示，在婴儿期最常见的表现是抽搐，而在婴儿期后则是运动发育迟缓和畸形。在 27 名患者中，诊断被延迟。尽管有依从性，开始治疗 12 岁以上的患者反应不佳。尽管 1,25（OH）2D 可能正常，但 1,25（OH）2D/25（OH）D 的抑制比值可能提供诊断线索。描述了各种区域特异性和热点反复出现的变异。具有截断变异的患者需要更高的每日骨化三醇需求和大大抑制 1,25（OH）2D/25（OH）D 的比值。
延迟诊断可能导致永久性身材矮小和畸形。与非截断变异相比，截断变异往往病情更严重。1,25（OH）2D/25（OH）D 比值的诊断准确性需要进一步验证。
