Physicians should be aware of
porphyrias, which could be responsible for unexplained gastrointestinal, neurologic, or skin disorders. Despite their relative rarity and complexity, most
porphyrias can be easily defined and diagnosed. They are caused by well-characterized
enzyme defects in the complex
heme biosynthetic pathway and are divided into categories of acute vs non-acute or hepatic vs
erythropoietic porphyrias. Acute
hepatic porphyrias (
acute intermittent porphyria,
variegate porphyria,
hereditary coproporphyria, and
aminolevulinic acid dehydratase deficient
porphyria) manifest in attacks and are characterized by overproduction of
porphyrin precursors, producing often serious abdominal, psychiatric, neurologic, or cardiovascular symptoms. Patients with
variegate porphyria and
hereditary coproporphyria can present with skin photosensitivity. Diagnosis relies on measurement of increased urinary 5-aminolevulinic
acid (in patients with
aminolevulinic acid dehydratase deficient
porphyria) or increased 5-aminolevulinic
acid and
porphobilinogen (in patients with other
acute porphyrias). Management of attacks requires
intensive care, strict avoidance of porphyrinogenic drugs and other precipitating factors, caloric support, and often
heme therapy. The non-
acute porphyrias are
porphyria cutanea tarda,
erythropoietic protoporphyria, X-linked protoporphyria, and the rare
congenital erythropoietic porphyria. They lead to the accumulation of
porphyrins that cause skin photosensitivity and occasionally severe liver damage. Secondary elevated urinary or blood
porphyrins can occur in patients without
porphyria, for example, in
liver diseases, or
iron deficiency. Increases in
porphyrin precursors and
porphyrins are also found in patients with lead intoxication. Patients with
porphyria cutanea tarda benefit from
iron depletion,
hydroxychloroquine therapy, and, if applicable, elimination of the hepatitis C virus. An α-
melanocyte-stimulating hormone analogue can reduce sunlight sensitivity in patients with
erythropoietic protoporphyria or X-linked protoporphyria. Strategies to address dysregulated or dysfunctional steps within the
heme biosynthetic pathway are in development.