Hereditary vitamin D-resistant rickets: a report of four cases with two novel variants in the VDR gene and successful use of intermittent intravenous calcium via a peripheral route

<jats:title>Abstract</jats:title><jats:sec id="j_jpem-2019-0466_s_999_w2aab3b7c35b1b6b1aab1c16b1Aa"><jats:title>Background</jats:title><jats:p>Hereditary vitamin D-resistant rickets (HVDRR) is caused by vitamin D receptor (VDR) defects. Patients with HVDRR do not respond to standard doses of calcitriol and oral calcium (Ca) treatment and need to be treated with intravenous Ca (IV-Ca) <jats:italic>via</jats:italic> a central route. However, central catheter-related complications can cause significant morbidity.</jats:p></jats:sec><jats:sec id="j_jpem-2019-0466_s_998_w2aab3b7c35b1b6b1aab1c16b2Aa"><jats:title>Case presentation</jats:title><jats:p>Four unrelated patients with HVDRR presenting with rickets and alopecia totalis were administered intermittent IV-Ca treatment (2–5 times/week) through a peripheral route. No complications such as infection, extravasation or arrhythmias were detected upon peripheral infusion. Peripheral 1–22 months’ duration of IV-Ca normalized parathyroid hormone (PTH) and alkaline phosphatase (ALP) in all patients, after which, oral Ca of 200–400 mg/kg/day and calcitriol of 0.5 μg/kg/day were sufficient to maintain normal PTH levels. Molecular studies on the <jats:italic>VDR</jats:italic> gene showed a previously reported homozygous c.454C > T (p.<jats:italic>Q152*</jats:italic>) pathogenic variant in two patients. Two novel homozygous variants in the other two patients were detected: (1) <jats:italic>c.756-2A > G</jats:italic>, which affects the splice acceptor site, and (2) <jats:italic>c.66dupG</jats:italic> (p.I23Dfs*20) variant leading to a frameshift that results in a premature stop codon.</jats:p></jats:sec><jats:sec id="j_jpem-2019-0466_s_997_w2aab3b7c35b1b6b1aab1c16b3Aa"><jats:title>Conclusions</jats:title><jats:p>Peripheral IV-Ca treatment is an effective and practical alternative treatment mode that provides dramatic clinical benefit in patients with HVDRR.</jats:p></jats:sec>