Oral Presentation ANZBMS-MEPSA-ANZORS 2022

Hypophosphatasia is a rare, genetic condition due to a loss of function mutation in tissue non-specific alkaline phosphatase (TNSALP). This results in low serum alkaline phosphatase (ALP) levels as well as accumulation of phosphocompounds (substrates of TNSALP), namely inorganic pyrophosphate (PPi), phosphoethanolamine (PEA), and pyridoxal-5-phosphate (PLP).  PPi in particular, is a potent inhibitor of bone mineralisation. Clinical manifestations of hypophosphatasia are broad, ranging from severe perinatal death in-utero to milder forms presenting in adulthood. Asfotase alfa is a human, recombinant TNSALP enzyme replacement therapy that was approved worldwide in 2015 and is indicated for paediatric onset hypophosphatasia.

We present the case report of a 64 years old female with childhood onset hypophosphatasia with complications of skull malformation requiring craniotomy, stress fractures requiring bilateral femoral fixation and new right tibial stress fracture, commencing on asfotase alfa enzyme replacement therapy. Within three months of initiation of treatment, her pain and mobility had significantly improved. Repeated imaging showed evidence of tibial fracture healing, thus no orthopaedic intervention was required. Health related quality of life measured using the SF-36 questionnaire showed improvement in domains of physical functioning, physical role limitations, vitality, social functioning, pain, emotional wellbeing and general health perceptions. Three months post treatment pathology tests had shown a reduction in urine phosphoethanolamine from 120mmol/mol creat to 26mmol/mol creat compared to pre-treatment baseline. Corrected calcium levels mildly reduced from 2.62mmol/L to 2.51mmol/L with treatment which has been reported in the literature and thought to be related to bone remineralisation. Local injection site reaction was the only side effect and responded well to antihistamine therapy.

Improvement in symptomology, biochemical markers as well as radiological evidence of fracture healing was seen within three months of initiation of asfotase alfa treatment in our patient with childhood onset hypophosphatasia with minimal side effects.