Bone Abstracts

Background: Vitamin D-dependent rickets type 1 (VDDR-1) is a rare autosomal recessive disorder caused by mutations in CYP27B1. This gene encodes the 1α-hydroxylase enzyme which converts 25-hydroxy vitamin D to the active form 1,25-dihydroxyvitamin D.

Objective: To describe a case of VDDR-1due to a novel CYP27B1 mutation.

Presenting problem: A 27-month-old female was admitted to the Pediatric Intensive Care Unit due to respiratory failure. She was born at term to consanguineous parents of Arab Muslim descent. Up until 8 months of age she was reportedly healthy, at which time hypotonia, distended abdomen and developmental delay were noted. She was hospitalized due to failure to thrive, clinical evidence of rickets and recurrent pneumonia episodes, the latest of which brought to respiratory failure and required mechanical ventilation. Due to failed repeated extubation attempts, she was transferred for further evaluation and treatment to our medical center. At admission, her weight was 7 kg (-4SD), height 72 cm (-4SD), and physical examination revealed a large anterior fontanel and palpable rachitic rosary. Blood tests: Calcium-6.9 mg/dl, phosphorus-1.3 mg/dl, magnesium-1.7 mg/dl, alkaline phosphatase-539 IU/l, PTH-521 pg/ml, 25hydroxyvitamin D-36.3 ng/ml, 1,25dihydroxyvitamin D-11 pg/ml. Urine amino acid profile showed significant aminoaciduria, suggestive of renal Fanconi. Radiographs of the skeleton revealed severe demineralization of the skeleton with multiple long bone fractures and vertebral compression fractures along with elongated frayed metaphyses of long bones and wide calvarial sutures. In order to pursue a molecular diagnosis, DNA was extracted from whole blood for whole exome sequencing.

Clinical management: Sequence analysis revealed a novel homozygous missense mutation, c.383C>T (p.T128I) in the CYP27B1 gene, confirming the diagnosis of VDDR-1. This mutation has not been previously reported and is predicted to be deleterious. The girl was treated with alfacalcidol, calcium and phosphor supplements and finally was extubated successfully.

Conclusion: Here we report a novel CYP27B1 mutation in child that presented with severe rickets and respiratory failure. Treatment with high doses of alfacalcidol lead to clinical improvement and allowed a successful extubation.

Disclosure: The authors declared no competing interests.