What is Acute Intermittent Porphyria (AIP)?

AIP is a rare genetic disorder affecting heme synthesis, causing episodic attacks of severe abdominal pain, neurological symptoms, and psychiatric disturbances. Attacks are often triggered by medications, fasting, or hormones.

Classic Attack Symptoms:

• Severe Abdominal Pain (90-95%): No peritoneal signs; often mistaken for acute abdomen
• Neurological: Peripheral neuropathy, muscle weakness, seizures, confusion
• Psychiatric: Anxiety, hallucinations, depression
• Autonomic: Tachycardia, hypertension, constipation
• Dark/Red Urine: From porphyrins (classic sign)
• Hyponatremia (SIADH)

Common Triggers:

• Medications: Barbiturates, sulfonamides, estrogen, many others
• Fasting/Low Carb Diets
• Hormonal Changes: Menstruation, pregnancy
• Alcohol
• Stress, Infection

Diagnosis:

• Urine Porphobilinogen (PBG): Markedly elevated during attack
• Urine Aminolevulinic Acid (ALA): Elevated
• Genetic Testing: HMBS gene mutation

Treatment:

• Acute Attack:
  • IV hemin (Panhematin®)—definitive treatment
  • IV dextrose (glucose suppresses heme synthesis)
  • Pain management (opioids—avoid unsafe drugs)
  • Treat hyponatremia if present
• Prevention:
  • Avoid triggers (unsafe medications, fasting)
  • High-carbohydrate diet
  • GnRH analogs for menstrual-triggered attacks
  • Prophylactic hemin for recurrent attacks
  • Givosiran (Givlaari®)—new RNAi therapy for prevention