A 28-year-old woman from rural Maharashtra presents to the emergency department with severe colicky abdominal pain, tachycardia (HR 110/min), and confusion. She reports a 3-day history of progressive abdominal distension and constipation. On examination, her abdomen is soft but distended; neurological exam reveals proximal muscle weakness and hyperreflexia. Urine dipstick is normal, but fresh urine left standing for 2 hours turns dark red-brown. Serum sodium is 118 mEq/L. Which of the following is the most likely diagnosis?

Explanation

## Diagnosis: Acute Intermittent Porphyria (AIP) ### Clinical Presentation This patient presents with the classic triad of acute porphyria: 1. **Acute neurovisceral crisis**: severe abdominal pain, constipation, tachycardia 2. **Neuropsychiatric manifestations**: confusion, proximal muscle weakness, hyperreflexia 3. **Hyponatremia**: due to SIADH (syndrome of inappropriate antidiuretic hormone secretion) ### Pathophysiology AIP is caused by deficiency of **porphobilinogen deaminase (PBGD)**, the third enzyme in heme synthesis. This leads to: - Accumulation of upstream precursors: **δ-aminolevulinic acid (ALA)** and **porphobilinogen (PBG)** - These neurotoxic precursors cause acute attacks triggered by: - Drugs (barbiturates, sulfonamides, oral contraceptives) - Fasting or metabolic stress - Infections - Menstrual cycle (in women) ### Diagnostic Clue: Dark Urine **Key Point:** Fresh urine turning dark red-brown on standing or exposure to light is pathognomonic for AIP. This occurs because PBG is oxidized to **porphobilin** (a dark polymer) in acidic urine exposed to light. ### Laboratory Findings in Acute Attack | Finding | Details | |---------|----------| | **Urine ALA & PBG** | Markedly elevated (diagnostic) | | **Serum sodium** | Low (SIADH-mediated) | | **Abdominal imaging** | Often normal (rules out surgical abdomen) | | **Urine dipstick** | Normal (PBG not detected by standard dipstick) | **High-Yield:** The normal dipstick with dark urine is a critical diagnostic clue that distinguishes porphyria from hematuria or myoglobinuria. ### Management of Acute Attack 1. **Avoid triggers**: discontinue precipitating drugs 2. **IV glucose or hemin**: suppresses ALA synthase, reducing precursor production 3. **Supportive care**: IV fluids, electrolyte correction (hyponatremia), analgesia (avoid morphine) 4. **Avoid**: barbiturates, sulfonamides, NSAIDs **Clinical Pearl:** Acute attacks can be life-threatening due to respiratory muscle paralysis (resembling Guillain-Barré syndrome) and severe hyponatremia. [cite:Robbins 10e Ch 7]