LAUSR

We present a case of a 22-month-old girl who was found to have an underlying metabolic bone disease as a cause for delayed gross motor development. The patient was referred to a district general hospital outpatient department as she was not yet cruising and had possible speech delay. However, she was crawling and had no fine motor or social developmental concerns. She had a normal birth history with no past medical or family history of note, her immunisations were up-to-date and she was on no medication. Examination showed her weight was on the 2nd-9th centile and her length was on the 0.4th centile. She had prominent notched clavicles with splayed wrists, mild scoliosis and a small thorax. She appeared to be in significant pain on hip abduction. Bloods showed a significantly raised alkaline phosphatase (5882), but low corrected calcium and phosphate. Her 25(OH)D3 was normal but her parathyroid hormone was raised. Radiographs were consistent with features of rickets and she had femoral, radial and ulnar fractures. After 1,25(OH)2D3 was returned as slightly low at 47, a diagnosis of 1-alpha-hydroxylase deficiency was made. She was commenced on oral alfacalcidol, calcium gluconate and phosphate. Upon review at 3 months, her biochemical markers were improved and she had made marked developmental progress. 1-alpha-hydroxylase deficiency was first identified in 1961 and is thought to be autosomal recessive with a mutation in the CYP27B1 gene, which prohibits conversion of 25(OH)D3 metabolite to the active 1,25(OH)2D3. Biochemical disturbance includes: moderate hypophosphataemia, severe hypocalcaemia, elevated parathyroid hormone and alkaline phosphatase, normal 25(OH)D3, and low 1,25(OH)2D3.Treatment aims to maintain corrected calcium levels within normal range by using large doses of 1,25(OH)2D3. The main concerns with treatment are nephrocalcinosis and intraocular calcification. Therefore, recommendations for monitoring are performing a bone profile, kidney function, parathyroid hormone and urinary calcium/creatinine ratio every 3 months and ophthalmology assessment, renal tract ultrasound and hand radiographs once per year.