Genetics, Pathophysiology, Diagnosis and Treatment
Edited by James C. Barton
Edited by Corwin Q. Edwards
Publisher: Cambridge University Press
Print Publication Year: 2000
Online Publication Date:August 2011
Chapter DOI: http://dx.doi.org/10.1017/CBO9780511666476.045
The term porphyria, derived from the Greek word porphyra, meaning purple, is apt because a hallmark of most of the porphyrias is the overexcretion of porphyrins in urine or feces. The porphyrins have a dark-red color that borders on purple. In most porphyrias, there are enzyme defects in the pathway of normal heme biosynthesis that cause the accumulation of porphyrins and porphyrin precursors. A summary of the pathway of heme biosynthesis showing the primary enzymatic defects in the porphyrias is displayed in Fig. 44.1. A classification of the porphyrias, emphasizing that either the liver or the bone marrow is the major site of overproduction of porphyrins and porphyrin precursors in these diseases, is shown in Table 44.1.
The major clinical features of the porphyrias are dermatologic and/or neurologic abnormalities. The types of porphyria in which dermatologic features predominate include porphyria cutanea tarda (PCT), the most common form of porphyria encountered world-wide. Hepatoerythropoietic porphyria is due to a rare, hereditary, severe deficiency in activity of the enzyme uroporphyrinogen decarboxylase (Uro-D), the enzyme that is also decreased in activity in PCT (Fig. 44.1). The severe deficiency in hepato-erythropoietic porphyria is due to homozygosity or compound heterozygosity for deficiency of Uro-D activity. Congenital erythropoietic porphyria (Günther's disease), also rare, is a form of usually severe cutaneous porphyria due to homozygous or compound heterozygous deficiency of the enzyme in the heme biosynthetic pathway immediately preceding Uro-D, namely, uroporphyrinogen III synthase (cosynthase).