Poster Session I (Abstracts 259 – 729)

The acute hepatic porphyrias (AHP), including acute intermittent\udporphyria (AIP), hereditary coproporphyria (HCP), and\udvariegate porphyria (VP), are due to a deficiency in the liver\udof one of the eight enzymes required for heme biosynthesis.\udInduction of the first enzyme 5-aminolevulinic acid synthase 1\ud(ALAS1) by triggers such as fasting or drug exposure can lead\udto accumulation of neurotoxic heme intermediates that result\udin acute life threatening neurovisceral attacks. Methods: We\udare currently performing a prospective, multinational, observational\udstudy to characterize the natural history and clinical\udmanagement of patients with AHP who experience recurrent\udattacks (> 3 attacks per year) or receive prophylactic treatment\udto prevent attacks. Patient porphyria disease activity questionnaires,\udphysical examinations, plasma and urinary porphyrin\udprecursors, circulating ALAS1 mRNA and health care utilization\uddata are collected at pre-specified intervals throughout the\ud6 month study. In addition, porphyria attack assessments and\udporphyrin precursor levels are collected during attacks. Interim\udResults: Enrollment is complete, but the study is ongoing. A\udtotal of 112 patients have been enrolled from 20 centers in\ud13 countries. The mean patient age is 39 years old, with the\udmajority being female (99F; 13M) and having a diagnosis of\udAIP (AIP=104; HCP=3; and VP=5) for a mean of 11.4 years.\udMost patients (85%) reported being treated previously with\udheme during an attack, while less than half (43%) reported taking\udheme prophylactically to prevent attacks. Patients reported\uda mean of 9.44 attacks (median 6; range 0-54) in the prior\udyear, of which approximately 70% required treatment in a\udhealthcare setting. The most common acute attack symptoms\udincluded abdominal pain (92%), nausea or vomiting (80%)\udand weakness (79%). Symptoms similar in character to those\udoccurring in attacks were reported chronically (i.e. all the time)\udin 46% of the patients. The baseline urinary porphobilinogen\udand aminolevulinic acid levels while patients were not having\udan acute attack were elevated at 34.9 mmol/mol Cr and 26.7\udmmol/mol Cr respectively (upper limit of normal: PBG < 1.2\udmmol/mol Cr; ALA < 3.1 mmol/mol Cr). Summary: This ongoing\udstudy should provide important information about the full\udspectrum of disease in AHP patients with recurrent attacks, as\udwell as provide insights into AHP pathophysiology and disease\udmanagement. The fact that close to half the patients have porphyria\udsymptoms all the time, even when not in the setting of\udan acute attack, suggests the disease is more chronic than previously\udappreciated. Additional 6-month data from this study\udwill be reported