Clinical characteristics and long-term management for patients with vitamin D-dependent rickets type II: a retrospective study at a single center in Saudi Arabia

Abstract

Introduction: Hereditary Vitamin D-dependent rickets type II (HVDDR-type II) is a rare autosomal recessive disorder caused by molecular variation in the gene encoding the vitamin D receptor (VDR). This study aims to evaluate phenotype and genotype characteristics and long-term follow-up of the largest group of patients with (HVDDR-type II) in Saudi Arabia.

Methodology: We conducted a retrospective chart review to collect the clinical, biochemical, and genetic data for all HVDDR-type II patients currently receiving treatment at King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia.

Results: A total of 42 patients, 57.1% female, and 42.9% male were included in the study. Seven patients were treated with high doses of oral calcium, while 35 patients were treated with IV calcium infusion. The median age at presentation was 15.5 months. Alopecia was found in 97.6%, 21.4% presented with bowing legs, 14.3% with delayed walking, 9.5% with seizure, and 2.4% presented with respiratory failure, while a family history of the disease was positive in 71.4% of total patients. Molecular genetic testing of the VDR gene in our cohort identified six different gene variants c.885 C>A (p.Tyr295Ter), c.88 C>T (p.Arg30Ter), c.1036G>A (p.Val346Met), c.820C>T (p.Arg274Cys), c.803 T>C (p.Ile268Thr), and c.2T>G (p.Met1?).

Conclusion: We are describing the largest cohort of patients with HVDDR-type II, their clinical biochemical findings, and the most prevalent genetic variants in our population.

Keywords: HVDD type II; alopecia; growth retardation; growth velocity; hereditary vitamin D rickets type II; vitamin D.

Figure 1

X-ray findings of 4-year-old male. (A) Before treatment, the images showing generalized decreased bone density, the profound widening of the growth plate with metaphyseal cupping and fraying of bilateral hips, ankles, knees, and wrists. Narrow chest wall with evidence of significant ricketic changes and costochondral junction fraying. (B) One year and a half after treatment (6 weeks IV calcium, then maintained on oral calcium 5 gm every 6 hours daily); showing interval improvement compared to the previously seen growth plate widening and metaphyseal irregularity/fraying, with interval metaphysical sclerosis in keeping with healing rickets. (Case 2 in the Supplementary File ).

Figure 2

Schematic representation of variants in the VDR gene identified in our cohort of Saudi patients with vitamin D-dependent rickets type II. The reference accession number for the VDR sequence is NM_001017535.2 and for the encoded protein is NP_001017535.1. Exons of the VDR gene are indicated by boxes and introns by interconnecting lines.

Figure 3

Growth chart of 16-years old male patient showing improvement in his growth with treatment (IV calcium) with genetic variant [c.803T>C (p.Ile268Thr)], (See the Supplementary Table , Case 23).