Acute Intermittent Porphyria

Acute Intermittent Porphyria (AIP) is an autosomal dominant metabolic disorder resulting from a deficiency in hydroxymethylbilane synthase (HMBS), an enzyme in the heme biosynthetic pathway. This deficiency leads to the accumulation of porphyrin precursors, particularly porphobilinogen (PBG) and aminolevulinic acid (ALA), in various tissues and fluids. Acute attacks are characterized by severe abdominal pain, neurological dysfunction (peripheral neuropathy, seizures, altered mental status), and psychiatric symptoms. These attacks are often triggered by factors such as certain medications, alcohol, stress, and hormonal changes. Diagnosis involves measuring urinary PBG and ALA levels, erythrocyte HMBS activity, and genetic testing for HMBS mutations. Treatment focuses on managing acute attacks with intravenous hemin arginate or givosiran to reduce porphyrin precursor production, along with supportive care for pain, nausea, and other symptoms. Long-term management involves avoiding triggers and, in some cases, prophylactic treatment with givosiran or liver transplantation for severe, recurrent attacks.