Acute Intermittent Porphyria: Signs and Symptoms
Acute intermittent porphyria (AIP) presents primarily with severe abdominal pain and neurological symptoms, representing the most common acute hepatic porphyria in the United States. 1
Core Clinical Manifestations
Neurovisceral Symptoms
The hallmark presentation of AIP during acute attacks includes:
- Severe abdominal pain - the most prominent symptom, often mimicking acute abdomen or bowel obstruction 1, 2
- Gastrointestinal symptoms including nausea, vomiting, constipation, or diarrhea 1, 3
- Neurological manifestations with peripheral neuropathy and muscle weakness 1
- Neuropsychiatric symptoms ranging from anxiety and confusion to seizures 3, 2
- Autonomic dysfunction presenting with tachycardia, hypertension, and sweating 2, 4
Metabolic and Systemic Features
- Hyponatremia occurs frequently during acute attacks 3, 4
- Dark or red-brown urine may develop, particularly when exposed to light, though urine can appear normal initially 1
- Electrolyte disturbances affecting water and electrolyte metabolism 5
Demographic and Temporal Patterns
- 90% of symptomatic patients are women, with attacks rarely occurring before menarche or after menopause 3
- Symptoms typically emerge in early adulthood (age range 19-45 years in clinical studies) 6, 7
- 90% of patients experience only one or few attacks in their lifetime 3
Precipitating Factors Context
In underweight individuals with nutritional deficiencies, specific triggers are particularly relevant:
- Reduced energy intake and fasting are major precipitants of acute attacks 8, 9
- Nutritional factors including low carbohydrate intake can trigger symptoms 2, 10
- Hormonal changes related to menstrual cycle, pregnancy (50% experience attacks during pregnancy/puerperium) 3
- Certain medications that induce hepatic cytochrome P450 enzymes (barbiturates, sulfonamides, certain anticonvulsants) 8
- Alcohol, smoking, and stress serve as additional precipitants 3, 9
Diagnostic Biochemical Markers
During an acute attack, urinary porphobilinogen (PBG) is markedly elevated to >10 times the upper limit of normal, which is pathognomonic for acute porphyria 1, 8. Normal PBG during symptoms excludes acute porphyria as the cause (except in extremely rare ALAD deficiency porphyria) 1.
- Urinary delta-aminolevulinic acid (ALA) is also elevated, though less specific than PBG 1
- PBG/ALA ratio is approximately 2:1 in AIP patients with normal renal function 1
- Chemical response (normalization of urinary ALA and PBG) occurs with appropriate treatment 7
Critical Clinical Pitfalls
The disease remains clinically latent in the majority of genetic carriers throughout life, with very low penetrance estimated at 0.5-1% for AIP 1, 10. This means most individuals with the genetic defect never develop symptoms, making clinical correlation with biochemical testing essential before diagnosis 1.
Attacks are frequently misdiagnosed as acute abdomen or bowel obstruction, leading to unnecessary surgical interventions 2. The combination of abdominal pain with neuropsychiatric symptoms and hyponatremia in the absence of other obvious causes should raise suspicion for AIP 4.