A 32-year-old woman presents to the emergency department with acute onset severe abdominal pain, tachycardia, and confusion. She has a history of recurrent similar episodes triggered by certain medications and fasting. Urine porphobilinogen (PBG) is markedly elevated during the acute attack. Which enzyme deficiency is the most common cause of her condition?

## Acute Intermittent Porphyria (AIP) — The Most Common Acute Porphyria ### Enzyme Defect **Key Point:** Porphobilinogen deaminase (PBGD), also called hydroxymethylbilane synthase (HMBS), deficiency causes acute intermittent porphyria (AIP), the most common acute hepatic porphyria. ### Pathophysiology PBGD catalyzes the third step of heme synthesis: 1. ALA → PBG (ALA dehydratase) 2. PBG → hydroxymethylbilane (PBGD) ← **DEFECT HERE** 3. Hydroxymethylbilane → uroporphyrinogen III Partial enzyme deficiency (50% activity) leads to: - Accumulation of upstream substrates (ALA and PBG) - Neurovisceral symptoms (abdominal pain, neuropsychiatric features, autonomic dysfunction) - Elevated urinary PBG and ALA (diagnostic hallmark) - **No photosensitivity** (unlike cutaneous porphyrias) ### Clinical Features of AIP | Feature | Details | |---------|----------| | **Acute attacks** | Severe colicky abdominal pain, vomiting, constipation | | **Neurological** | Confusion, seizures, peripheral neuropathy, respiratory paralysis | | **Autonomic** | Tachycardia, hypertension, fever | | **Triggers** | Drugs (barbiturates, sulfonamides, OCPs), fasting, stress, infection | | **Urine** | Dark/port-wine colored during attacks (PBG + ALA elevated) | | **Photosensitivity** | Absent (differentiates from porphyria cutanea tarda) | ### Inheritance & Epidemiology - **Autosomal dominant** with incomplete penetrance - ~80% of carriers remain asymptomatic - Females > males (hormonal triggers) - **Most common acute porphyria** worldwide **High-Yield:** AIP = elevated PBG + ALA + acute neurovisceral symptoms + NO skin lesions = PBGD deficiency. ### Management During Acute Attack 1. Avoid precipitating factors (offending drugs) 2. High-carbohydrate diet (glucose suppresses ALA synthase) 3. IV dextrose or hematin (inhibits ALAS1) 4. Supportive care (seizure prophylaxis with gabapentin, NOT barbiturates) **Clinical Pearl:** Always screen for porphyria before prescribing barbiturates, sulfonamides, or estrogens in patients with recurrent abdominal pain and neuropsychiatric symptoms.