O01 Hypophosphatasia in adults at a specialist centre in the UK: the spectrum of musculoskeletal disease

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Abstract Background Hypophosphatasia (HPP) is a condition arising due to mutations in the gene encoding the tissue-non-specific alkaline phosphatase (TNSALP) isoenzyme (ALPL), leading to deficient activity of TNSALP. It can be inherited as an autosomal dominant or recessive disorder. There are over 300 known mutations in the ALPL gene associated with HPP, leading to varying degrees of deficiency in the activity of TNSALP. There are six clinical forms of HPP, with a great degree of heterogeneity in clinical presentation. The adult form is generally milder than perinatal and infantile forms, which may be fatal. Estimates of the prevalence of HPP range from 0.3/100,000 (more severe forms), to 1/6370 (less severe forms). Diagnosis is based on clinical features, biochemical abnormalities (low serum alkaline phosphatase (ALP), raised serum pyridoxal-5’-phosphate and raised urinary phosphoethanolamine), and genetic testing. The dentition and musculoskeletal system are often affected. Low trauma, metatarsal and atypical subtrochanteric femoral fractures may be seen, often with poor healing. However in some cases, individuals may present with calcium pyrophosphate deposition disease (CPPD) or non-specific musculoskeletal features. Under-recognition of HPP and diagnostic delay are therefore common. This retrospective observational study, performed at a specialist centre, aimed to characterise the spectrum of musculoskeletal manifestations in adults with HPP. Methods Patient records of adults with a confirmed diagnosis of HPP seen in the Rheumatology department at St George’s Hospital, London, were consulted. Clinical features at presentation and those developed subsequently were recorded, with a focus on musculoskeletal manifestations. Biochemical, genetic and radiographic data were also obtained. Results Fifteen individuals (two male, thirteen female) with a confirmed diagnosis of HPP were identified. Average delay to diagnosis was 21 years. The commonest presenting feature for the whole cohort was joint pain or swelling, followed by dental caries. The commonest presenting musculoskeletal feature in childhood was fracture (often low trauma and recurrent); in adults it was joint pain followed by poor mobility. There were eight diagnoses of osteoarthritis, five cases of tendinopathy and three of bursitis. Four patients had previously been diagnosed with psoriatic arthritis and three with pseudogout. Other musculoskeletal diagnoses included patellofemoral dysfunction, hypermobility and musculoskeletal tumours (two individuals). The upper limb joints were most commonly affected; some individuals reported back and knee pain. Musculoskeletal morbidity was high: eight individuals had poor mobility or abnormal gait, and three were unable to work through ill health. Conclusion There is a long delay to diagnosis of HPP. The condition may present in adults with non-specific musculoskeletal or dental features. It is therefore important to consider the diagnosis in individuals with a low ALP and musculoskeletal features which may suggest HPP, such as fractures or CPPD. Earlier recognition may avoid potential harm through inappropriate bisphosphonate or high-dose vitamin D therapy. Disclosures J. Kotecha None. S. Mansour None. C. Hall None. K.E. Moss None.