Bone Abstracts

Background: Asfotase alfa therapy improves clinical outcome in young children with severe form of hypophosphatasia (HPP). Treatment outcome in older children (≥12 years) has not been reported.

Presenting problem: We report clinical outcome of a 16 year-old male with childhood HPP who started enzyme therapy at age 15 years.

Clinical management: The patient was diagnosed with HPP at age 2 years when he presented with premature loss of primary teeth and genu varum. He had a history of multiple fractures requiring 16 orthopaedic surgeries with rod and pin placement in his lower extremities. He had chronic skeletal pain and used cane to ambulate with great difficulty. He presented to Endocrine Clinic at age 15 years with height of 126.4 cm (Z score −4.7, height age 7.5 years), arm span 139 cm, weight 25.2 kg (Z −5.78), Tanner stage 3 for pubertal development. He had severe scoliosis and deformity of both legs. Serum alkaline phosphatase level was <20 U/l, with elevated pyridoxal 5’-phosphate (836.8 nmol/l; normal 20–125). Bone age was delayed at 12.5 years with marked metaphyseal fraying and lucency in distal radius and ulna. He was started on asfotase alfa 2 mg/kg Q20 3 times/week. He had marked clinical improvement in growth and mobility with no report of pain after 3 months of treatment. At 6 month follow up, he walked without cane and became more sociable and liked to play outdoor with peers. Bone radiograph at 6 months showed striking improvement in previous lucency areas. At 9 months, height was 133.5 cm (growth velocity of 9.5 cm/year), while arm span increased to 148 cm (growth velocity of 12 cm/year). However, at 12 months, he was noted to have worsening scoliosis from 70 degrees before therapy to 110 degrees, with slightly decreased height at 129.5 cm, necessitating a scoliosis surgery. His lumbar bone density improved from baseline of 0.319 to 0.381 gram/cm² at 1 year (height-adjusted Z score decreased from −2.7 to −3.1).

Discussion: Treatment with asfotase alfa for 1 year significantly improved growth, physical function, pain, overall quality of life and skeletal radiographic findings in this patient.

Disclosure: The authors declared no competing interests.