Porphyrias

Porphyrias are a group of rare inherited or acquired disorders resulting from defects in the heme biosynthesis pathway. The faulty enzymes cause accumulation of porphyrins or their precursors in the liver, bone marrow, blood, or skin, leading to a range of clinical manifestations. Porphyrias are broadly categorized by the primary site of excess—hepatic porphyrias (liver) and erythropoietic porphyrias (bone marrow)—and by whether their symptoms are predominantly neurovisceral or cutaneous.

Acute hepatic porphyrias include acute intermittent porphyria, hereditary coproporphyria, variegate porphyria, and, rarely, delta-aminolevulinic acid dehydratase deficiency porphyria. They typically cause neurovisceral attacks with abdominal pain, nausea, vomiting, tachycardia, hypertension, and neurologic or psychiatric symptoms. Triggers such as certain drugs, fasting, alcohol, or hormonal changes can precipitate attacks. Porphyrin precursors may appear in urine during attacks.

Erythropoietic porphyrias, such as congenital erythropoietic porphyria (Gunther disease) and erythropoietic protoporphyria, mainly cause cutaneous photosensitivity. CEP presents in infancy with blistering and mutilation of sun-exposed skin; EPP causes marked photosensitivity with painful, burning reactions to light but less severe systemic symptoms. Laboratory findings include elevated porphyrins or protoporphyrin in erythrocytes or plasma.

Porphyria cutanea tarda, the most common porphyria, typically presents with blistering and fragility of sun-exposed skin and is associated with liver disease and iron overload. Diagnosis relies on porphyrin measurements in urine, blood, and stool, along with genetic testing in some cases.

Management emphasizes avoidance of triggers, careful use of drugs, and specific therapies such as intravenous hemin for acute attacks, glucose loading, and measures to reduce liver iron or treat liver disease. Skin protection is essential for cutaneous porphyrias.