Update on the diagnosis and management of the autosomal dominant acute hepatic porphyrias. Issue 8 (18th May 2022)

• Record Type: Journal Article
• Authors: Schulenburg-Brand, Danja; Stewart, Felicity; Stein, Penelope; Rees, David; Badminton, Mike
• Is Part Of: Journal of clinical pathology. Volume 75:Issue 8(2022)
• Page Start: 537
• Page End: 543
• Publication Date: 2022-05-18
• Subjects: BIOCHEMISTRY -- DIAGNOSIS -- LIVER; Pathology -- Periodicals; Pathology, Molecular -- Periodicals; 616.0705
• DOI: 10.1136/jclinpath-2021-207647
• Languages: English
• ISSNs: 0021-9746

Abstract

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.