porphyriasmetabolic

Porphyrias are a group of inherited or acquired metabolic disorders caused by defects in the enzymatic steps of heme biosynthesis. The resulting buildup of porphyrins and their precursors in body tissues leads to a range of symptoms that can affect the liver, bone marrow, skin, nerves, and eyes. The term “metabolic porphyria” is often used to emphasize disorders driven by defects in the heme-producing pathway rather than external causes alone.

Porphyrias are commonly classified by the primary tissue where the defect manifests—hepatic (liver) or erythropoietic (bone marrow)—and by clinical presentation as acute neurovisceral or cutaneous forms. Acute hepatic porphyrias include acute intermittent porphyria, hereditary coproporphyria, variegate porphyria, and, less commonly, aminolevulinic acid dehydratase deficiency porphyria. Cutaneous hepatic porphyrias include porphyria cutanea tarda and hepatoerythropoietic porphyria. Erythropoietic porphyrias, such as congenital erythropoietic porphyria and erythropoietic protoporphyria, primarily cause skin photosensitivity and erythroid abnormalities.

Pathophysiology involves specific enzyme defects in the heme synthesis pathway, causing accumulation of neurotoxic precursors like delta-aminolevulinic acid and porphobilinogen during attacks and excess porphyrins in the skin for cutaneous forms. Clinical features vary: acute attacks produce severe abdominal pain, nausea, autonomic instability, and neuropsychiatric symptoms; cutaneous forms cause blistering and fragility of sun-exposed skin; erythropoietic forms lead to lifelong photosensitivity and anemia.

Diagnosis relies on measuring porphyrins and their precursors in urine, plasma, and feces, along with genetic testing. Management focuses on avoiding triggers, acute treatment with intravenous hemin and supportive care, and disease-specific strategies such as phlebotomy or low-dose hydroxychloroquine for some cutaneous forms. Prognosis varies by subtype and severity, with most patients achieving control through ongoing management.