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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.
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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.
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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 ...