A166 ANALYSIS OF SYMPTOMS, DIAGNOSTIC PATTERNS, AND CANADIAN PROVIDER PERSPECTIVE OF ACUTE HEPATIC PORPHYRIA

Abstract

Abstract Background Acute hepatic porphyria (AHP) is a family of rare genetic diseases, the most common being acute intermittent porphyria (AIP). AHP results from enzyme deficiencies involved in haem synthesis, leading to accumulation of neurotoxic haem intermediates, aminolaevulinic acid (ALA) and porphobilinogen (PBG), causing potentially life-threatening attacks and chronic symptoms. Patients afflicted by AHP often remain without a proper diagnosis for up to 15 years due to lack of awareness and testing. First-line diagnostic biochemical tests include measuring spot urinary ALA and PBG as both are elevated in the majority of AHP patients. Aims The study aimed to describe physicians experience diagnosing AHP and characterize patients globally, including Canada. Methods Physicians (n=175) who actively managed AHP patients (with and without recurrent attacks) in the preceding year were recruited from 9/2017–10/2017 to complete an online survey collecting information on demographics, familiarity with AHP and diagnostic tests, perspective on symptoms important to diagnosis, referral patterns, and treatment preferences. Physicians also completed a chart review of 546 patients and reported anonymized data on demographics, medical history, attacks, and symptoms. Data was analysed using descriptive statistics. Results Canadian physicians (n=15) practiced a mean of 19.7 years, 67% worked in community settings, and 53% were gastroenterologists. Symptoms informing AHP diagnosis included fatigue (93%), sensory loss (87%), mental confusion (87%), Abdominal pain (80%), red/dark urine (80%), vomiting (73%). AHP diagnostic tests considered informative for diagnosis included urinary ALA (87%) and PBG (80%); however, several non-specific tests were also commonly considered informative of AHP. Chronic symptoms reported included fatigue (75%), nausea/vomiting (70%), weakness (66%), pain (58%), anxiety (54%), diarrhea (41%), constipation (40%). Canadian physicians reported a mean of 58% AHP patients they manage being initially misdiagnosed. Global patients (n=546) were aged 40 years (mean), female (52%), with AIP (83%). Canadian patients (n=38) were aged 41 years (mean), female (61%), with AIP (78%). Patients had mean of 3.4 attacks and 1.6 hospitalizations in the past year. Conclusions This study highlights the challenges diagnosing AHP due to non-specificity of symptoms and limited understanding of diagnostic procedures. Due to the frequent presentation of gastrointestinal symptoms, AHP should be included in gastroenterologists’ differential diagnosis of patients presenting with non-specific abdominal pain. Among patients diagnosed with AHP, both acute attacks and chronic symptoms were reported, implicating both in the disease. Funding Agencies Alnylam Pharmaceuticals