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The porphyrias are a group of inherited and acquired metabolic disorders, each resulting from the deficient activity of a specific enzyme in the heme biosynthetic pathway.1,2 These enzyme deficiencies are inherited as autosomal dominant or recessive traits, with the exception of porphyria cutanea tarda (PCT), which usually is sporadic. These disorders are classified as either hepatic or erythropoietic, depending on the primary site of overproduction and accumulation of the porphyrin precursor(s) or porphyrin(s) (Table 167-1). Although some have overlapping features, manifestations of the hepatic porphyrias are neurological, including abdominal pain, neuropathy, and mental disturbances, whereas the erythropoietic porphyrias characteristically cause cutaneous photosensitivity. The neurological involvement in the hepatic porphyrias, which typically presents after puberty, results from the hepatic production of a neurotoxic metabolite, as liver transplantation ameliorated the frequent attacks in a patient with acute intermittent porphyria (AIP).3 Cutaneous sensitivity to sunlight may occur in infancy because of the excitation of excess porphyrins in the skin by long-wave ultraviolet light, which leads to cell damage, scarring, and deformation. Steroid hormones, drugs, and nutrition influence the production of porphyrin precursors and porphyrins, thereby precipitating or increasing the severity of some porphyrias.

Table 167-1 Clinical, Metabolic, and Genetic Characteristics of the Human Porphyrias

Rare homozygous variants of the autosomal dominant hepatic porphyrias have been identified and usually manifest clinically before puberty. The symptoms in these patients are usually more severe and occur earlier than those of patients with the respective autosomal dominant porphyria (see below).1,4 Thus, the porphyrias are actually ecogenic disorders in which environmental, physiological, and genetic factors interact to cause disease.

Many symptoms of the porphyrias are nonspecific, and diagnosis is often delayed. Laboratory testing can confirm or exclude the diagnosis of a porphyria. Table 167-1 summarizes the major metabolites that accumulate in each porphyria. Urinary 5′-aminolevulinic acid (ALA) and porphobilinogen (PBG) are easily quantitated ...

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