Porphyrinurias

Porphyrinurias are a group of disorders characterized by abnormal porphyrin metabolism, leading to excessive excretion or accumulation of porphyrins and their precursors in urine. They can be inherited or acquired and are broadly classified into acute (neurovisceral) porphyrias and cutaneous porphyrias.

Acute porphyrias include acute intermittent porphyria, hereditary coproporphyria, variegate porphyria, and, rarely, delta-aminolevulinic acid dehydratase deficiency porphyria. In these disorders hepatic heme synthesis is disrupted, causing accumulation and urinary excretion of precursors such as delta-aminolevulinic acid and porphobilinogen during attacks. Patients commonly experience abdominal pain, nausea, vomiting, neuropathy, autonomic dysfunction, and anxiety; attacks may be triggered by drugs, hormones, fasting, or illnesses. Urine may darken or give a red-brown color after exposure to light and air.

Cutaneous porphyrias include congenital erythropoietic porphyria, porphyria cutanea tarda, and erythropoietic protoporphyria. These disorders cause photosensitivity due to accumulation of specific porphyrins that generate reactive oxygen upon light exposure, leading to blistering, itching, hyperpigmentation, and, in some forms, severe scarring. Erythropoietic protoporphyria typically causes immediate or near-immediate pain with sun exposure rather than blistering.

Diagnosis relies on quantitative and qualitative measurements of urinary porphyrins and their precursors, supported by plasma and stool analyses and genetic testing to identify the responsible enzyme defect. Management is tailored to the type: acute attacks are treated with intravenous heme therapy and glucose loading, while provoking factors are avoided. Cutaneous forms emphasize sun protection and, in select conditions, measures such as phlebotomy or iron management. Prognosis varies by form, with potential lifelong morbidity in cutaneous porphyrias and potentially life-threatening attacks in acute porphyrias.