P074 Diagnostic Journeys of Patients with Hypophosphatasia
Authors: Marsden Duncan , Ridley Raphaella 
Published: April 2024

Background/Aims

Hypophosphatasia (HPP) is an ultra-rare genetic disorder characterised by low activity of tissue non-specific alkaline phosphatase (TNAP). Due to heterogeneity of clinical presentation and lack of definitive biochemical testing, misdiagnosis and diagnostic delay are common.

Methods

We used information reported by HPP patients to the Rare and Undiagnosed Diseases Study (RUDY) online registry (www.rudystudy.org). We included patients with a self-reported diagnosis of HPP and information on at least one of our outcomes. We described their diagnostic journey, including diagnostic delays, initial symptoms, incorrect diagnoses and healthcare professionals seen.

Results

16 participants with a self-reported diagnosis of HPP were included in the analysis with 14/16 female. Of those reporting the date of initial symptom onset, 9/14 participants had symptom onset before the age of 18, whereas five had symptom onset in adulthood. The median time from symptom onset to HPP final diagnosis was 26.5 years (N = 8, IQR 11.2 to 34.6). From the first GP visit related HPP to final diagnosis the median time was 9.5 years (N = 6, IQR 6.2 to 11.1), and from the first hospital visit related to HPP, the median time to final diagnosis was 3.9 years (N = 10, IQR 0.8 to 10.5). Among participants reporting initial symptoms (N = 13), 16 categories of initial symptom were reported, with a median of two initial symptom categories per participant (IQR 1 to 2). The most prevalent initial symptom was pain (10/13, 77%). Of these 10 participants, four had lower limb pain, one had upper limb pain, one had back pain, and five had pain of unspecified location. Skeletal deformity at birth, dental manifestations, joint swelling, and infantile feeding problems were each present in 2/13 participants (15%). Among participants reporting whether they had received other diagnoses prior to that of HPP (N = 13), nine participants (75%) received at least one other diagnosis, with diagnoses of 10 different conditions reported across the cohort. The most common other diagnosis was fibromyalgia (4/13, 31%), followed by hypermobility (2/13, 15%). 21 different types of healthcare professionals were seen prior to final diagnosis. General Practitioners were the most commonly consulted (9/14, 64%). This was followed by allied health professionals (8/14, 57%). Of the eight participants seeing allied health professionals, all eight saw physiotherapists, and 4 (29% of total) also saw at least one other allied health professional. Other types of healthcare professional seen by multiple responders included orthopaedic surgeons (5/14, 36%), rheumatologists (5/14, 36%), geneticists (4/14, 29%), endocrinologists (3/14, 21%), metabolic specialists (3/14, 21%) and dentists (2/14, 14%).

Conclusion

Patients typically present with a cluster of symptoms, often including pain, and are often seen by general practitioners and physiotherapists before diagnosis. Increasing awareness of HPP in these professions may improve early recognition of the disease.

Disclosure

D. Marsden: None. R. Ridley: None.