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 abdominal pain, constipation, and progressive neuropsychiatric symptoms including anxiety and hallucinations. On examination, she is hypertensive (BP 160/95 mmHg), has a distended abdomen with no peritoneal signs, and demonstrates proximal muscle weakness. Urine dipstick shows no blood or protein. Serum sodium is 125 mEq/L (hyponatremia). Urine collected during the acute episode turns dark red-brown on standing. Which of the following is the most likely diagnosis?

Explanation

## Clinical Diagnosis: Acute Intermittent Porphyria (AIP) ### Key Clinical Features Matching This Case **Key Point:** Acute intermittent porphyria presents with the classic triad of: 1. **Acute neurovisceral crisis** — severe colicky abdominal pain, constipation, ileus 2. **Neuropsychiatric manifestations** — confusion, anxiety, hallucinations, proximal muscle weakness (neuropathy) 3. **Autonomic instability** — tachycardia, hypertension, hyponatremia (SIADH) ### Pathophysiology **High-Yield:** AIP is an autosomal dominant deficiency of **porphobilinogen deaminase (PBGD)** [also called hydroxymethylbilane synthase (HMBS)], the third enzyme in the heme synthesis pathway. This leads to: - Accumulation of 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 - Hormonal changes (menstrual cycle) ### Diagnostic Clues in This Case | Feature | Why It Points to AIP | |---------|---------------------| | **Dark red-brown urine on standing** | Porphobilinogen oxidizes to porphobilin (dark pigment) — pathognomonic for acute porphyrias | | **Abdominal pain + constipation** | Autonomic neuropathy affecting GI smooth muscle | | **Proximal muscle weakness** | Acute motor neuropathy (can progress to respiratory failure) | | **Hyponatremia + hypertension** | SIADH from CNS involvement | | **Neuropsychiatric symptoms** | ALA and PBG are neurotoxic; mimic psychiatric illness | | **NO skin photosensitivity** | Rules out porphyria cutanea tarda and erythropoietic protoporphyria | ### Diagnostic Confirmation **Clinical Pearl:** During an acute attack, measure: - **Urine PBG and ALA** — markedly elevated (>10× normal) - **Plasma PBG** — elevated - **Fecal porphyrins** — may be normal or slightly elevated in AIP (unlike variegate porphyria) ### Management of Acute Attack ```mermaid flowchart TD A[Acute Porphyria Attack]:::outcome --> B[Stop triggering agent]:::action A --> C[Supportive care]:::action C --> D[IV dextrose 300-500g/day]:::action C --> E[Avoid fasting]:::action A --> F{Severe attack?}:::decision F -->|Yes| G[IV Hemin 3-4 mg/kg daily]:::action F -->|No| H[Symptomatic management]:::action G --> I[Suppresses ALA synthase]:::outcome H --> J[Analgesia, antiemetics, benzodiazepines]:::action ``` **High-Yield:** Hemin (or heme arginate) is the specific treatment for severe attacks — it suppresses ALA synthase-1 via negative feedback, reducing precursor accumulation. ### Why NOT the Other Options **Variegate porphyria:** Also presents with acute neurovisceral crisis, BUT: - Has **skin photosensitivity** (bullae, fragility on sun-exposed areas) — absent here - Fecal porphyrins are markedly elevated (not just urine) **Porphyria cutanea tarda:** - Presents with **chronic photosensitive skin lesions** (blistering, hyperpigmentation, scarring) — NOT acute neurovisceral crisis - NO acute abdominal or neuropsychiatric symptoms **Erythropoietic protoporphyria:** - Causes **acute photosensitivity** (burning pain on sun exposure, urticaria) — NOT abdominal pain - NO neurovisceral or psychiatric symptoms - Urine remains normal color **Mnemonic: ACUTE PORPHYRIA = AIP** - **A**cute neurovisceral (abdominal pain, constipation, ileus) - **C**onfusion and psychiatric symptoms - **U**rine turns dark (PBG oxidation) - **T**achycardia and hypertension - **E**levated ALA and PBG - **P**roximal muscle weakness (neuropathy) - **O**utcomes: respiratory failure if untreated - **R**emember: autosomal dominant PBGD deficiency - **P**recipitants: drugs, fasting, stress, menses - **H**emin is treatment - **Y**ellow-brown urine (PBG) - **R**are but life-threatening - **I**nhibit ALA synthase - **A**void triggers [cite:Robbins 10e Ch 7]