## Acute Intermittent Porphyria (AIP) ### Enzyme Defect **Key Point:** AIP is caused by deficiency of **porphobilinogen deaminase (PBGD)**, also called hydroxymethylbilane synthase (HMBS), the third enzyme in the heme synthesis pathway. **High-Yield:** PBGD deficiency leads to accumulation of upstream precursors: **δ-aminolevulinic acid (ALA)** and **porphobilinogen (PBG)**, which are neurotoxic. ### Clinical Features | Feature | Details | |---------|----------| | **Inheritance** | Autosomal dominant (50% penetrance) | | **Acute attacks** | Abdominal pain, neuropsychiatric symptoms, autonomic dysfunction | | **Triggers** | Drugs (barbiturates, sulfonamides), fasting, stress, menstruation, infections | | **Urine** | Dark red/burgundy color (due to porphobilinogen); positive Watson-Schwartz test | | **Cutaneous signs** | **Absent** (distinguishes AIP from porphyria cutanea tarda) | ### Management of Acute Attack 1. **Glucose infusion** (inhibits ALA synthase) 2. **Hemin/heme arginate** (potent feedback inhibitor of ALAS) 3. Avoid triggering drugs 4. Supportive care (pain, seizure control) **Clinical Pearl:** The mnemonic **"ABCDEFG"** lists drugs that precipitate AIP: **A**lcohol, **B**arbiturates, **C**arbamazepine, **D**apsone, **E**rythromycin, **F**enfluramine, **G**riseofulvin. **Mnemonic:** **AIP = Acute Intermittent Porphyria = Abdominal + Acute + Accumulation of ALA/PBG** (no skin photosensitivity) [cite:Harrison's Principles of Internal Medicine 21e Ch 414]
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