Endocrine Abstracts

We present the first paediatric patient treated with Asfotase Alfa (AA) or ‘Strensiq’, for perinatal Hypophosphatasia (HPP), who has turned 16 and approaches the end of her time in paediatric care. She is the child with the longest treatment duration worldwide. We reflect on the 16 years of learning she has provided for endocrinologists globally. HPP is a rare, inherited, metabolic bone disease, characterised by defective bone and teeth mineralisation. It is caused by mutations in the ALPL gene which reduce the activity of the enzyme Tissue Nonspecific Alkaline Phosphatase ‘TNSALP’. Previously perinatal HPP was a lethal condition. In 2022, NICE recommended AA, (a bone targeted enzyme replacement therapy), as a treatment option. Our patient was born at 38+5 weeks. In-utero multiple fractures were detected. Postnatally she had a low ALP (17U/l) and following a grossly abnormal skeletal survey and genetic testing, she was diagnosed with HPP. At 5 months old her length and weight were <0.4^th centile. She was hypotonic, vomiting, and irritable. An updated skeletal survey demonstrated progressive deterioration of the mineralisation status of her whole skeleton with fractures of upper and lower limbs and ribs. She was admitted for symptom control and felt to be in the end stages of her disease. Following discussion with the paediatric metabolic bone team in Sheffield, she flew to Winnipeg and enrolled as patient 01-01 in the ENB 002-08 study, the first trial of Recombinant ‘TNSALP’ enzyme replacement. She started AA treatment in October 2008, initially intravenously then a 3 times weekly subcutaneous dose. She deteriorated on the initial 1 mg/kg dose but improved on 2 mg/kg. She returned home 22 weeks later and remains on AA. The course for patients surviving into adulthood with perinatal HPP is complicated, despite treatment with AA. This patient has associated morbidity - scoliosis, craniosynostosis, short stature, nephrocalcinosis and bilateral femoral bowing. She awaits further elective surgery. AA is allowing patients who would have previously died in infancy to survive into adulthood. This patient is sitting her GCSEs and plans to be a nurse. This case serves as a reminder to us of the importance of clinical research.