Affiliation:
1. Department of Genetics and Genomic Sciences Icahn School of Medicine at Mount Sinai New York New York USA
2. Department of Medicine, Division of Hematology and Oncology University of Washington Seattle Washington USA
3. Department of Integrative Biomedical Sciences, Division of Medical Biochemistry and Structural Biology University of Cape Town Cape Town South Africa
4. Division of Hepatology, Department of Medicine, Faculty of Health Sciences University of Cape Town and Groote Schuur Hospital Cape Town South Africa
5. Department of Haematological Medicine King's College Hospital London UK
Abstract
AbstractThe acute hepatic porphyrias (AHPs) include three autosomal dominant disorders, acute intermittent porphyria, variegate porphyria and hereditary coproporphyria, and the ultra‐rare autosomal recessive 5‐aminolevulinic acid dehydratase‐deficient porphyria. All four are characterized by episodic acute neurovisceral attacks that can be life‐threatening if left untreated. The attacks are precipitated by factors that induce hepatic 5‐aminolevulinic acid synthase 1 (ALAS1), resulting in accumulation of the porphyrin precursors, 5‐aminolevulinic acid and porphobilinogen, which are believed to cause neurotoxicity. Diagnosis of these rare disorders is often delayed because the symptoms are non‐specific with many common aetiologies. However, once clinical suspicion of an AHP is raised, diagnosis can be made by specialized biochemical testing, particularly during attacks. Moderate or severe attacks are treated with intravenous hemin infusions, together with supportive care to relieve pain and other symptoms. Prophylactic treatments are recommended in patients with confirmed recurrent attacks (≥4 attacks in a maximum period of 12 months), the most effective being givosiran, an RNAi therapeutic targeting hepatocyte ALAS1 mRNA. AHP patients with clinically and/or biochemically active disease are at elevated risk for developing long‐term complications, including chronic kidney disease, chronic hypertension and hepatocellular carcinoma, thus, surveillance is recommended. Here, using a case‐based format, we provide an update on the pathogenesis, diagnosis and treatment of the AHPs based on literature review and clinical experiences.
Funder
National Institute of Diabetes and Digestive and Kidney Diseases
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
1. Porphyrins and the porphyrias;Liver International;2024-09-09