Acute Intermittent Porphyria (Porphyria)

Acute Intermittent Porphyria (AIP) – Treatment Options

Introduction
Acute intermittent porphyria (AIP) is a rare autosomal dominant metabolic disorder caused by deficiency of porphobilinogen deaminase, leading to accumulation of porphyrin precursors (aminolevulinic acid [ALA] and porphobilinogen [PBG]). It presents with acute neurovisceral attacks: severe abdominal pain, neuropathies, psychiatric symptoms, autonomic dysfunction, and hyponatremia. Attacks are often precipitated by medications, hormonal changes, alcohol, or fasting. Treatment focuses on aborting acute attacks, preventing recurrences, and long-term risk reduction.

1. Immediate Management of Acute Attacks

• Hospital admission for monitoring and supportive care.

• Intravenous glucose (10%–20%): High-dose carbohydrate infusion (300–500 g/day) can suppress ALA synthase activity in mild attacks.

• Hemin therapy (gold standard):

  • Intravenous hemin (hemin arginate or lyophilized hematin): 3–4 mg/kg/day for 4 days.

  • Restores hepatic heme pool and downregulates ALA synthase, halting toxic precursor accumulation.

2. Supportive and Symptomatic Therapy

• Pain control:

  • Opioids (morphine, fentanyl) often required for severe pain.

  • Avoid unsafe drugs (e.g., barbiturates, sulfonamides).

• Nausea/vomiting: Ondansetron or metoclopramide (porphyria-safe).

• Autonomic dysfunction: Beta-blockers (propranolol) for tachycardia and hypertension.

• Hyponatremia (SIADH-related): Fluid restriction, hypertonic saline in severe cases.

• Seizures: Gabapentin, benzodiazepines (safe choices). Avoid phenytoin, carbamazepine, and valproate, which are porphyrinogenic.

3. Prevention of Recurrent Attacks

• Trigger avoidance:

  • Avoid porphyrinogenic drugs (barbiturates, sulfonamides, antiepileptics, rifampicin, estrogens).

  • Limit alcohol intake, manage stress, avoid prolonged fasting or ketogenic diets.

• Hormonal control (in women with cyclical attacks):

  • Gonadotropin-releasing hormone (GnRH) analogs to suppress ovulation.

• Prophylactic hemin infusions: For patients with frequent recurrent attacks.

• Givosiran (RNA interference therapy):

  • Silences hepatic ALA synthase-1 gene expression.

  • Reduces attack frequency and urinary ALA/PBG levels in patients with recurrent AIP.

4. Long-Term and Supportive Care

• Monitoring: Regular assessment of renal and liver function (due to increased long-term risk of chronic kidney disease and hepatocellular carcinoma).

• Genetic counseling: For affected families.

• Dietary management: Adequate carbohydrate intake to avoid catabolic states.

• Liver transplantation: Considered in severe refractory cases as a curative option.

5. Multidisciplinary Care

• Hematologists/metabolic specialists: For acute attack management and long-term therapy.

• Neurologists: For neuropathy and seizure management.

• Nephrologists/hepatologists: For chronic complications (CKD, HCC).

• Genetic counselors: For family risk assessment and education.