ESPE Abstracts

Background: Calcium homeostasis is primarily regulated by vitamin D. In the absence of the active hormone or a functional receptor, bones are inadequately mineralized, leading to the development of rickets. Vitamin D-dependent rickets type 2 (VDDR2) is a rare autosomal recessive disorder caused by mutations in the vitamin D receptor (VDR) gene.

Case Report: A 12-months-old girl was transported to the local hospital ED with a three-minute 1^st episode of seizures: unconsciousness, hypotonia, ocular reversion, cyanosis, and sialorrhoea. There was no history of trauma, accidental drug ingestion, fever, or other infectious signs. During the patient’s stabilization, capillary blood gas showed severe hypocalcaemia (Ca++ 0,76 mmol/l) without hypomagnesaemia. Intravenous (iv) calcium gluconate was administrated. On further examination, she had total alopecia, closed anterior fontanelle, dentition according to her age, enlarged wrists, and bowed legs. Parents were nonconsanguineous. Pregnancy and delivery were unremarkable. She had alopecia since birth and was not yet able to walk, even with support. Additional blood evaluation showed severe hypocalcaemia, hyphosphataemia, hyperparathyroidism, increased alkaline phosphatase (ALP), and markedly elevated 1,25(OH)₂D. 25(OH)D was in the normal range. Full body skeleton X-ray showed diffuse bone demineralization, “rosary ribs”, and metaphysis flaring, fraying, and cupping. Renal ultrasound was normal. VDDR2 was presumed and iv calcium gluconate was titrated up to a maximum of 1,15mmol/kg/day. After calcium stabilization, oral calcium carbonate was started (1g/day), with progressive increasing dosage (maximum 6g/day) and parallel reduction of calcium gluconate, which was suspended after 2 months. Calcitriol (maximum 21µg/day) was also started with significant improvement in calcaemia and gradual reduction in PTH and ALP. Genetic analysis found a homozygous mutation c.133A>G p.(Lys45Glu) in the VDR gene, confirming VDDR2. Nine months after discharge, and exclusively on oral therapy, calcium levels have been moderately stable (total calcium: 8,7 to 9,7mg/dl). PTH and ALP still have an oscillatory profile, but with a downward trend and near reference range levels.

Discussion: Genetic mutations cause about 13% of rickets cases. VDDR2 secondary to Lys45Glu mutation prevents VDR from activating gene transcription. High levels of 1,25(OH)₂D and alopecia are the distinct points of this disease. Alopecia is thought to be a sign of disease severity. Control of secondary hyperparathyroidism is the therapeutic goal, decreasing bone demineralization. Intravenous calcium treatment for several months, followed by high doses of oral calcium and calcitriol, seems to be an effective approach.