Acute hepatic porphyria: A rare but critical diagnosis

ABSTRACT Acute hepatic porphyria (AHP) is a rare genetic disorder resulting from disruptions in hepatic heme biosynthesis, leading to the accumulation of neurotoxic porphyrins, aminolevulinic acid (ALA) and porphobilinogen (PBG). This accumulation causes acute and chronic neurovisceral symptoms, significantly affecting patient quality of life. Diagnosis is often delayed due to the rarity and nonspecific presentation of AHP, with biochemical and genetic testing serving as key diagnostic tools. For patients with recurrent attacks, prophylactic strategies aim to reduce episode frequency and severity. Although intravenous hemin remains the primary treatment for acute attacks, a major advancement in AHP management is givosiran, a small interfering ribonucleic acid therapy that reduces ALAS1 expression, thereby lowering ALA and PBG levels and decreasing attack frequency. Results from the ENVISION trial demonstrated a 70% reduction in porphyria attacks among patients receiving givosiran compared with placebo, leading to its Food and Drug Administration approval in 2019. Effective management of AHP includes addressing complications such as chronic pain, fatigue, neuropathy, and an increased risk of primary liver cancer. Patient education, medication management, and preventive strategies, including trigger avoidance and early symptom recognition, are critical in improving outcomes. Support groups and patient advocacy networks provide additional resources to enhance disease coping and adherence to care plans. With early diagnosis and comprehensive management, individuals with AHP can mitigate complications and maintain a better quality of life.