Acute intermittent porphyria
Formal Definition
Acute intermittent porphyria (AIP) — an autosomal dominant disorder of heme biosynthesis caused by partial deficiency of porphobilinogen deaminase (hydroxymethylbilane synthase), in which affected individuals typically have baseline enzyme activity 50% of normal but remain asymptomatic unless triggered by factors that upregulate heme synthesis (drugs that induce CYP450, alcohol, fasting, hormonal fluctuations, infection, stress) — building up upstream intermediates porphobilinogen and δ-aminolevulinic acid (ALA), which are neurotoxic; presents with the "5 Ps" — Painful abdomen, Polyneuropathy, Psychological symptoms, Port wine-colored urine, Precipitated by drugs/alcohol/fasting; commonly misdiagnosed initially as cholecystitis, appendicitis, or psychiatric illness.
How It's Used on the Ward
"Acute porphyria" — the elusive diagnosis that presents as abdominal pain, hyponatremia, neuropathy, and altered mental status in a young person; positive family history or known precipitation by a drug (barbiturates, rifampin, sulfonamides, estrogen) suggests the diagnosis; treatment is IV glucose and heme arginate; many standard analgesics are dangerous.
Example
""26-year-old woman, G1P1, postpartum 6 weeks, presents to ED with severe diffuse abdominal pain, vomiting, mild confusion, and new lower-extremity weakness progressing over 6 hours. Exam: tender but soft abdomen, no peritoneal signs, BP 142/88, HR 108, motor weakness 3/5 in lower extremities, urine bag is port-wine-colored. Labs: hyponatremia (Na 124), mild transaminitis, normal lipase, normal CT abdomen, CBC normal. Urine PBG and ALA markedly elevated. Trigger: rifampin started 2 weeks ago for postpartum mastitis prophylaxis in a patient with no known porphyria history. Diagnosis: acute intermittent porphyria triggered by rifampin. Treated with IV dextrose 10% at 200 mL/hr, then heme arginate 3-4 mg/kg/day IV x4 days; weakness resolves, abdominal pain resolves, electrolytes normalize.""
Clinical Context
Pathophysiology: deficiency of porphobilinogen deaminase (third enzyme in heme biosynthesis pathway) → accumulation of upstream ALA and porphobilinogen → neurological symptoms (likely through neurotoxic effects of ALA on neurons); red pigment (porphobilinogen) oxidizes on standing → red/port-wine urine. Triggers (drugs): barbiturates, sulfonamides, rifampin, phenytoin, carbamazepine, oral contraceptives, alcohol, ergots, dichloralphenazone, primidone, griseofulvin, pyrazinamide, hydantoins, estrogens/progestins, ergot alkaloids. Trigger (other): fasting, low-carbohydrate diet, smoking, infection, stress, menstruation, pregnancy. Diagnosis: urine PBG (porphobilinogen) markedly elevated during attack (often 10-100× normal); spot urine test for PBG is good initial screen; 24-hour urine for quantitative PBG and ALA during attack. Treatment: (1) Stop offending trigger. (2) IV glucose high-dose (300-500g/day) — feedback inhibition of ALA synthase. (3) IV heme arginate or hematin — definitive treatment, suppresses ALAS for sustained period. (4) Symptomatic: pain control with safe opioids (avoid barbiturates), nausea control (ondansetron safe), anxiety (lorazepam safe). Counseling: lifetime list of safe vs unsafe medications; identify personal triggers; family screening for AIP.