A 28-year-old woman presents to the emergency department with acute severe abdominal pain, tachycardia (HR 110/min), and confusion. She has a history of similar episodes triggered by fasting and certain medications. Physical examination reveals dark urine and hypertension (BP 160/95 mmHg). Serum electrolytes show hyponatremia (Na⁺ 128 mEq/L) and hypokalaemia (K⁺ 3.2 mEq/L). Urine porphobilinogen (PBG) is markedly elevated. What is the most likely diagnosis?

Explanation

## Diagnosis: Acute Intermittent Porphyria (AIP) ### Clinical Presentation This patient presents with the classic acute neurovisceral crisis of AIP: - **Acute abdominal pain** (often severe and mimics surgical abdomen) - **Neuropsychiatric symptoms** (confusion, anxiety, psychosis) - **Autonomic instability** (tachycardia, hypertension) - **Dark urine** (due to porphobilinogen and δ-aminolevulinic acid) - **Electrolyte abnormalities** (hyponatremia from SIADH, hypokalaemia) ### Biochemical Basis **Key Point:** AIP is caused by deficiency of porphobilinogen deaminase (PBGD, also called hydroxymethylbilane synthase [HMBS]), the third enzyme in heme synthesis. This leads to proximal accumulation of δ-aminolevulinic acid (ALA) and porphobilinogen (PBG). **High-Yield:** The markedly elevated urinary PBG is the hallmark diagnostic finding in acute attacks of AIP. Plasma PBG and ALA are also elevated during acute episodes. ### Pathophysiology of Acute Attack 1. Heme depletion → loss of feedback inhibition on ALA synthase 2. Massive accumulation of neurotoxic precursors (ALA, PBG) 3. ALA and PBG are neurotoxic → peripheral neuropathy, autonomic dysfunction, CNS effects 4. Neurological manifestations: confusion, seizures, psychosis, weakness 5. Autonomic crisis: hypertension, tachycardia, arrhythmias ### Triggers for Acute Attacks - **Medications:** Barbiturates, sulfonamides, oral contraceptives, phenytoin, carbamazepine - **Fasting/caloric restriction** (decreases heme synthesis) - **Stress, infection, menstruation** - **Alcohol** ### Management of Acute Attack 1. **Avoid triggering factors** (especially offending drugs) 2. **IV glucose (500 g/day) or IV hemin (3–4 mg/kg)** — both suppress ALA synthase 3. **Supportive care:** IV fluids, electrolyte correction, seizure prophylaxis (benzodiazepines safe; avoid barbiturates) 4. **Symptomatic management:** Analgesia, antiemetics **Clinical Pearl:** Hemin is the most effective agent during acute crisis; it directly inhibits ALA synthase and rapidly suppresses porphyrin precursor synthesis. ### Mnemonic for Acute Porphyria Triggers: **CHAMP** - **C** — Carbamazepine, Contraceptives - **H** — Hypoglycaemia, Hormonal changes - **A** — Alcohol, Antibiotics (sulfonamides) - **M** — Menstruation, Medications (barbiturates) - **P** — Phenytoin, Porphyria (stress) ### Comparison Table: Acute vs. Cutaneous Porphyrias | Feature | Acute Intermittent Porphyria | Porphyria Cutanea Tarda | Erythropoietic Protoporphyria | | --- | --- | --- | --- | | **Enzyme defect** | PBGD (HMBS) ↓ | UROD ↓ | Ferrochelatase ↓ | | **Acute neurovisceral crisis** | **Yes** (hallmark) | No | No | | **Photosensitivity** | No | Yes (blistering, scarring) | Yes (burning pain in sun) | | **Urine PBG** | ↑↑↑ (during attack) | Normal or ↑ | Normal | | **Fecal porphyrins** | ↑ (coproporphyrin) | ↑ (uroporphyrin) | ↑ (protoporphyrin) | | **Dark urine** | Yes (acute attacks) | Yes (chronic) | No | | **Inheritance** | Autosomal dominant | Mostly acquired (Type I) | Autosomal dominant | **High-Yield:** AIP is the most common acute porphyria and presents with **neurovisceral symptoms without photosensitivity**. The other acute porphyrias (variegate and hereditary coproporphyria) can also present with acute attacks but are less common. ### Why Variegate Porphyria is NOT the Answer While variegate porphyria (deficiency of protoporphyrinogen oxidase) can present with acute attacks similar to AIP, it is **less common** and often has **photosensitive features** (skin blistering) in addition to acute symptoms. The clinical presentation here is classic for AIP without skin manifestations.