A 28-year-old woman from rural Maharashtra presents with acute onset severe abdominal pain, tachycardia, and confusion following exposure to sulfonamide antibiotics. She has a family history of recurrent neuropsychiatric episodes. Clinical suspicion is high for acute intermittent porphyria (AIP). Which investigation is most appropriate to confirm the diagnosis during the acute attack?

Explanation

## Diagnostic Approach to Acute Intermittent Porphyria **Key Point:** During an acute attack of AIP, urinary porphyrin precursors (ALA and PBG) are markedly elevated and are the gold standard for diagnosis. ### Why Urine ALA and PBG? **High-Yield:** AIP is characterized by acute neurological and psychiatric symptoms triggered by precipitants (drugs, fasting, stress, infection). The acute attack involves: - Overproduction of δ-aminolevulinic acid synthase (ALAS) - Massive elevation of ALA and PBG in urine (often 10–100× normal) - These precursors are neurotoxic and cause the acute syndrome **Clinical Pearl:** Urine PBG turns dark red or burgundy on standing or exposure to light due to spontaneous polymerization to porphobilin — a classic bedside finding. ### Timing of Testing | Investigation | Timing | Sensitivity in Acute Attack | | --- | --- | --- | | **24-hour urine ALA + PBG** | During acute attack | ~95% | | Serum porphyrins | During attack | Low sensitivity; levels may be normal | | Erythrocyte protoporphyrin | Chronic/between attacks | Not useful for AIP diagnosis | | Plasma porphyrins | Less specific | Elevated in cutaneous porphyrias, not AIP | **Mnemonic:** **ACUTE** porphyrias (AIP, VHAP, ALAD) → **URINE** precursors (ALA + PBG); **CUTANEOUS** porphyrias (PCT, EPP) → **BLOOD/FECAL** porphyrins. ### Confirmatory Step Once acute attack is confirmed by elevated urine ALA/PBG, genetic testing for PBGD (porphobilinogen deaminase) mutations can confirm the diagnosis between attacks.