ESPE Abstracts

Introduction: Vitamin D-dependent rickets (VDDR) describes a group of genetic disorders characterized by early-onset rickets that develops due to insufficient concentration of active forms of vitamin-D or unresponsiveness to active vitamin D. The aim of this study was to share the clinical features and long-term outcome of cases followed up in our center with the diagnosis of either VDDR-Type-1 and VDDR-Type-2.

Method: Presenting complaints, demographic-anthropometric measurements, laboratory and radiological examinations, molecular genetic analysis results and treatment responses were obtained from patient records and reviewed retrospectively.

Results: Ten patients from eight families were included. Eight cases had a diagnosis of VDDR-Type-1 and two cases had a diagnosis of VDDR-Type-2. The median (range) age of diagnosis was 20 (14-52) months. The most common complaints were delayed walking (n=9), skeletal deformities (n=8) and short stature (n=6). Molecular genetic analysis revealed 1319–1325dupCCCACCC(Phe443Profs*24) duplication mutation in five of eight cases with VDDR-Type-1. A case diagnosed with VDDR-Type-2 had alopecia and the novel pathogenic variant NM_00117536.2c.352_356delGACAG (p.I118Qfs*29) (p.Ile118GlnfsTer29) (Homozygous) was detected in the VDR gene. All cases had received vitamin D prophylaxis and/or treatment before diagnosis. The mean±SD serum 25-hydroxy-vitamin-D (25OHD3) at diagnosis was 47.1±9.6 ng/mL. Calcitriol at a mean dose of 25.2±3.8 ng/kg and calcium treatments when necessary were given in all cases. After a mean follow-up period of 8.2±2 years, significant improvement was observed in biochemical and anthropometric measurements (Table 1). No nephrolithiasis/nephrocalcinosis was detected in any of the patients on urinary system ultrasonography.

Conclusion: Rare genetic types of rickets should be considered in the diagnostic approach, even if short stature is not present in cases unresponsive to vitamin D therapy or with normal 25OHD3 levels. These cases should be referred to Pediatric Endocrinology clinics. Improvements in biochemical and anthropometric measurements show that calcitriol treatment was effective and safe in these cases.

Abbreviations: SD, standard deviation; ALP, alkaline phosphatase; PTH, parathyroid hormone; SDS, standard deviation score.