Clinical Management of Porphyric Disorders

Porphyric disorders encompass a spectrum of inherited abnormalities in the haem‐biosynthetic pathway, broadly classified into hepatic and erythropoietic subtypes. Acute hepatic porphyrias (AHP) present with neurovisceral crises characterised by severe abdominal pain, neuropathic symptoms and autonomic dysfunction. Management of acute attacks centres on immediate removal of precipitating factors, high‐carbohydrate infusions to suppress δ‐aminolevulinic acid synthase activity and intravenous haem preparations to replenish hepatic haem pools. Analgesics, antiemetics and cardiovascular support are integral to symptomatic control. In patients with recurrent attacks, prophylactic regimens include regular haem infusions or RNA interference therapy to downregulate hepatic precursor overproduction. Chronic surveillance targets complications such as systemic hypertension, chronic kidney disease and hepatocellular carcinoma, with imaging and biochemical monitoring instituted from mid‐adulthood. Refractory cases may be considered for orthotopic liver transplantation, which is curative for hepatic overproduction but carries procedural risks. Erythropoietic protoporphyria (EPP) manifests predominantly with painful photosensitivity due to protoporphyrin accumulation in erythrocytes and the skin. Preventive strategies focus on strict light avoidance, physical sunscreens and, in some patients, oral β‐carotene supplementation. Regular assessment of liver function and biliary imaging is essential to detect early cholestatic injury. Severe hepatic involvement may warrant sequential liver and bone‐marrow transplantation to correct both hepatic and erythroid defects.

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Technical terms

Acute hepatic porphyria (AHP): A group of inherited hepatic enzyme defects leading to accumulation of neurotoxic haem precursors and episodic neurovisceral crises.

Porphobilinogen (PBG): A porphyrin precursor whose urinary elevation signifies active acute porphyria.

Haemin: An iron‐containing haem derivative administered intravenously to repress hepatic δ‐aminolevulinic acid synthase activity and abort acute attacks.

Givosiran: An RNA interference therapeutic designed to silence hepatic δ‐aminolevulinic acid synthase 1 mRNA, thereby preventing precursor overproduction.

Erythropoietic protoporphyria (EPP): An inherited disorder of erythroid haem synthesis resulting in protoporphyrin accumulation, photosensitivity and risk of hepatic injury.

Photosensitivity: Cutaneous phototoxic reaction induced by accumulated porphyrins on exposure to visible or ultraviolet light.

References

1. AGA Clinical Practice Update on Diagnosis and Management of Acute Hepatic Porphyrias: Expert Review. Gastroenterology (2023).
2. Efficacy and safety of givosiran for acute hepatic porphyria: 24‐month interim analysis of the randomized phase 3 ENVISION study. Liver International (2021).
3. Erythropoietic protoporphyria. Orphanet Journal of Rare Diseases (2009).
4. Liver transplantation for acute intermittent porphyria is complicated by a high rate of hepatic artery thrombosis. Liver Transplantation (2012).