What forms of rickets do not respond to treatment with vitamin D?

Vitamin D dependent rickets type I (VDDR I) also known as VDDR IA or pseudovitamin D deficiency ricket type 1 (PDDR) is due to defective 1α-OHase (CYP27B1) activity leading to deficiency of biologically active form of vitamin D–calcitriol. The treatment usually is calcitriol 10–20 ng/kg/day in a single or two divided doses. Another rare condition is a defect in vitamin D 25-hydroxylation due to mutation in the CYP2R1 gene (also termed vitamin D-dependent rickets type 1B (VDDR IB).

Vitamin D-dependent rickets type II (VDDR II) also variably termed VDDR IIA or hereditary vitamin D-resistant rickets (HVDRR) which is due to resistance to the activated form of vitamin D, (calcitriol), usually manifests with rickets and features of alopecia and is associated with very high levels of calcitriol. The genetic defect is at the level of vitamin D receptor (VDR). The VDDR IIB is due to an abnormal nuclear ribonucleoprotein that interferes with the vitamin D receptor-DNA interaction, leading to a phenotype similar to VDDR IIA with end-organ resistance to active vitamin D but a normal vitamin D receptor.

Management usually consists of high doses of calcitriol 1–6 μg/kg/day with supplemental calcium 1–3 g elemental daily, with the aim to achieve normocalcemia, to maintain PTH levels within normal limits and to avoid hypercalciuria. Some patients may require intravenous calcium supplementa- tion 0.4–1.4 g elemental calcium/m2/day to normalize calcium. Some patients with this form of rickets may spontaneously outgrow the defect as they enter puberty. Other forms of rickets such as hypophosphatemic rickets or other causes listed previously need to be considered when a patient with rickets does not respond to vitamin D therapy.

Normal phosphorus levels in children

• 0–5 days—4.8–8.2 mg/dL

• 1–3 year—3.8–6.5 mg/dL

• 4–11 years—3.7–5.6 mg/dl

• 12–15 year—2.9–5.4 mg/dL

• 16–19 year—2.7–4.7 mg/dL