What are the symptoms of porphyria?

Symptoms of Porphyria

Porphyrias present with a wide array of clinical manifestations ranging from severe neuropsychiatric symptoms requiring specialized intensive care to chronic skin symptoms including bullae on sun-exposed areas or acute painful photosensitivity, depending on the specific type of porphyria. 1

Types of Porphyria and Their Primary Symptoms

Acute Hepatic Porphyrias

• Acute Intermittent Porphyria (AIP): Primarily presents with severe abdominal pain, nausea, vomiting, constipation, neurological symptoms, and neuropsychiatric manifestations 1, 2
• Variegate Porphyria (VP): Presents with both acute neurovisceral attacks and bullous skin lesions 1
• Hereditary Coproporphyria (HCP): Similar to VP with both neurovisceral symptoms and skin manifestations 1
• ALA-Dehydratase Deficiency Porphyria: Extremely rare, presents with abdominal pain and neurological symptoms 1

Cutaneous Porphyrias

• Porphyria Cutanea Tarda (PCT): Most common porphyria, characterized by bullous skin lesions, skin fragility, and scarring 1
• Erythropoietic Protoporphyria (EPP): Presents with acute painful photosensitivity without scarring 1, 3
• X-linked Erythropoietic Protoporphyria (XLEPP): Similar to EPP with acute painful photosensitivity 1
• Congenital Erythropoietic Porphyria (CEP): Presents with severe bullous skin lesions and hemolytic anemia 1

Detailed Symptom Presentation

Neurovisceral Symptoms (Acute Porphyrias)

• Severe abdominal pain (most common presenting symptom) 3, 2
• Nausea and persistent vomiting 3, 4
• Constipation 3, 5
• Hyponatremia (can be severe) 3, 4
• Peripheral neuropathy (indicates severe attack) 3, 6
• Neuropsychiatric manifestations including anxiety, confusion, hallucinations, and psychosis 3, 7
• Autonomic dysfunction (tachycardia, hypertension) 5, 6
• Seizures (in severe cases) 3, 4

Cutaneous Symptoms

• Bullous type: Fragile skin with blisters that rupture easily, scarring, and hyperpigmentation on sun-exposed areas (PCT, VP, HCP, CEP) 1
• Acute painful photosensitivity: Immediate burning, stinging, or itching upon sun exposure without blistering (EPP, XLEPP) 1, 3
• Skin changes typically appear on sun-exposed areas (face, hands, forearms) 1, 8

Long-term Complications

• Liver disease including primary liver cancer and acute liver failure 1, 8
• Chronic kidney disease and renal failure 1, 3
• Hypertension 1, 3
• Osteoporosis 1, 3
• Vitamin D deficiency 1, 3
• Anemia 1

Clinical Patterns and Considerations

• Symptoms of acute porphyrias typically become symptomatic in early adulthood 1, 2
• Cutaneous porphyrias like PCT most often present in adults or older age 1
• Erythropoietic porphyrias (EPP, CEP) may present in childhood or even infancy 1
• 90% of symptomatic acute porphyria patients are women, with attacks rare before menstruation or after menopause 3
• Acute attacks can be triggered by medications, alcohol, fasting, hormonal changes, stress, and infections 4, 8
• Urine may turn red-brown when exposed to light during an acute attack due to porphobilinogen oxidation 1

Diagnostic Considerations

• Clinical symptoms alone are insufficient for diagnosis; biochemical testing is essential 2, 8
• During acute attacks, urinary porphobilinogen (PBG) and delta-aminolevulinic acid (ALA) are significantly elevated 1, 4
• For cutaneous symptoms, plasma fluorescence scanning is a useful first-line test 1
• Symptoms may mimic many other disorders, leading to frequent misdiagnosis 6, 7

Important Caveats

• Symptoms vary widely between different types of porphyria and even within the same type 1, 6
• Symptoms can fluctuate with periods of remission and exacerbation 5, 7
• Acute porphyria attacks can be life-threatening if not promptly diagnosed and treated 4, 6
• 90% of patients with acute porphyria experience only one or few attacks in their lifetime 3
• Lead poisoning and hereditary tyrosinemia can present with similar symptoms to acute porphyrias 1