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Update on the diagnosis and management of the autosomal dominant acute hepatic porphyrias
  1. Danja Schulenburg-Brand1,
  2. Felicity Stewart2,
  3. Penelope Stein3,
  4. David Rees3,4,
  5. Mike Badminton1
  1. 1Medical Biochemistry and Immunology, University Hospital of Wales Healthcare NHS Trust, Cardiff, UK
  2. 2School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK
  3. 3Haematological Medicine, King's College London, London, UK
  4. 4School of Cancer and Pharmaceutical Sciences, King's College London, London, UK
  1. Correspondence to Dr Danja Schulenburg-Brand, Medical Biochemistry and Immunology, University Hospital of Wales Healthcare NHS Trust, Cardiff CF14 4XW, UK; Danja.Schulenburg-brand{at}wales.nhs.uk

Abstract

The autosomal dominant acute hepatic porphyrias (AHPs), acute intermittent porphyria, hereditary coproporphyria (HCP) and variegate porphyria (VP), are low penetrance adult onset disorders caused by partial deficiency of enzymes of haem biosynthesis. All are associated with acute neurovisceral attacks, which are a consequence of the increased hepatic demand for haem triggered by hormones, stress, drugs or systemic infections which leads to upregulation of the pathway and overproduction of haem precursors 5-aminolaevulinic acid (ALA) and porphobilinogen (PBG). Acute episodes are characterised by severe abdominal pain, nausea, vomiting, hyponatraemia, hypertension and tachycardia, behavioural disturbance and can progress to include seizures, peripheral motor neuropathy and posterior reversible encephalopathy syndrome if undiagnosed and untreated. VP and HCP may also present with photocutaneous skin lesions either alone or during acute symptoms. Diagnosis involves demonstrating increased excretion of PBG in urine. Treatment focuses on removing or managing triggers, supportive treatment and suppressing the hepatic haem pathway by administering human haemin. Chronic complications include hypertension, chronic kidney disease and hepatocellular carcinoma. A small proportion of symptomatic patients with AHP progress to repeated acute attacks which require preventative therapy. A new RNA interference therapy has recently been licensed and is likely to become the treatment of choice in this situation.

  • BIOCHEMISTRY
  • DIAGNOSIS
  • LIVER

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Footnotes

  • Handling editor Patrick J Twomey.

  • Contributors DS-B: concept and design, coauthored Diagnostic approach section, authored tables and graphs and take-home messages and edited drafts. FS: authored Introduction, Genetics and epidemiology and Pathogenesis and precipitating factors sections and edited drafts. DR: authored Clinical features of acute neurovisceral attacks and Long-term complications of AHPs sections. PS: authored Treating an acute attack and Specific patient groups and areas of risk sections. MB: authored Abstract and coauthored the Diagnostic approach sections and edited the drafts. All authors were involved in reviewing the drafts and DS-B, MB and FS prepared responses for referees.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Commissioned; externally peer reviewed.

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