Bone Abstracts (2015) 4 P155 | DOI: 10.1530/boneabs.4.P155

Hydroxylase (CYP27B1) deficiency presenting with marked hypotonia, growth failure, hypoventilation, pulmonary hypertension and a renal proximal tubulopathy

John Barton1, Wesley Hayes2 & Christine Burren1


1Department of Paediatric Endocrinology, Bristol Royal Hospital for Children, Bristol, UK; 2Department of Paediatric Nephrology, Bristol Royal Hospital for Children, Bristol, UK.


Background: 1α-hydroxylase is a mitochondrial P450 enzyme critical to the synthesis of active calcitriol from the pro-hormone 25(OH) D. Multiple different mutations in the CYP27B1 gene have been identified that abolish or reduce 1α-hydroxylase enzymatic activity resulting in vitamin D dependent rickets type 1. Children with 1α-hydroxylase deficiency present with a clinical picture of joint pain and deformity, hypotonia, muscle weakness, growth failure and sometimes hypocalcaemic seizures or fractures in early infancy. We report on a Black-African child with a typical presentation, although the unusual additional feature of renal proximal tubulopathy.

Presenting problem: Male infant was referred aged 12 months with faltering growth (length and weight measurements below 0.4th centile), hypotonia and delayed gross motor development. He had been breast fed until aged 9 months. His mother had taken vitamin supplements during pregnancy and the child was on a standard vitamin D preparation. On examination he was also noted to have a small chest, subcostal recession and a mild thoracolumbar scoliosis.

Investigation results were consistent with rickets: Calcium 1.78 mmol/l, Phosphate 0.68 mmol/l, Alkaline Phosphatase 1970 IU/l, Parathyroid hormone 49.5 pmol/l, yet 25(OH) D was 87.5 nmol/l. Renal function was normal. Skeletal radiographs revealed generally demineralised bones with coarse trabeculae and widespread periosteal reaction. Metacarpal and rib fractures and a thoracolumbar kyphoscoliosis were identified. He was noted to have a mild metabolic acidosis, generalised aminoaciduria and increased renal excretion of B2 Microglobulin. White cell cystine was normal. Plasma 1α,25-dihydroxyvitamin D3 levels were found to be inappropriately low (55.6 pmol/l).

Clinical management: He required high dose 1α-Hydroxycholecalciferol therapy (200 μ/kg per day) and calcium supplements over 4 months to normalise bone chemistry, initiate bone healing (evident radiologically), improve linear growth and significantly improve motor development. Progress was complicated by on-going feeding difficulties and mild hypoxaemia during sleep with associated pulmonary hypertension requiring low-flow O2 therapy. His acidosis and aminoaciduria resolved entirely.

Discussion: We present a 12 months boy with severe 1α Hydroxylase (CYP27B1) deficiency associated with a reversible renal proximal tubulopathy and cardiopulmonary complications. The precise nature of action of 1α,25-dihydroxyvitamin D3 in proximal tubular cells is not well understood.

Disclosure: The authors declared no competing interests.

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