Porphyria cutanea tarda (PCT) is a human metabolic disorder due to an impaired activity of uroporphyrinogen decarboxylase (URO-D), the fifth enzyme of the heme biosynthetic pathway. Four types of PCT are commonly recognized: sporadic PCT (s-PCT, type I) with URO-D deficiency restricted to the liver, familial PCT (f-PCT, type II) with enzyme deficiency present in all cells, hereditary PCT (f-PCT, type III) with proven familiarity and normal URO-D in erythrocytes and toxic PCT (type IV) caused by exogenous chemical agents inhibiting hepatic URO-D activity. The classification of inherited and non-inherited forms of PCT was suggested on the basis of URO-D measurement in red blood cells. The outcome of the clinical manifestations of PCT is often precipitated by several triggering factors such as hepatic siderosis, alcohol and drugs abuse, estrogens, virus infections and hepatotoxic chemicals. The action mechanism of exogenous factors in lowering enzyme activity is still a matter of debate. The aim of this study was to measure the erythrocyte URO-D activity in a large sample of Italian PCT patients in order to define the enzyme level distribution and to attempt a correlation between enzyme activity, clinical parameters and risk factors. A total of 133 PCT patients ( 126 males, 7 females; age 23-88 yrs), diagnosed on the basis of mild to severe cutaneous lesions and elevated urinary porphyrins excretion were studied. URO-D activity, iron parameters, HCV positivity and other risk factors were assessed for each patient. Erythrocyte URO-D activity was measured spectrofluorometrically and the reaction product was quantified by reverse-phase HPLC. The normal values obtained from 40 healthy controls were 5.7 ±0.7 coproporphyrinogen/h/mg prot with values ranging from 4.5 to 7.8 that were designated as lower and upper cut-off to define different classes of enzyme activity. By analizing the 133 PCT subjects we found 32 samples (24%) below the lower value (Class I). 82 (62%) within the normal range (Class II) and 19 (14%) with increased enzyme activity (Class III). Considering the relation between different classes of enzyme activity and clinical parameters we did not observe significant differences but a lower presence of HCV infection (63% vs 84%) in Class I as compared with Classes II and III and a gradual decrease of urinary porphyrin levels with the higher values of UROD activity. This study has been useful to assess the prevalence of the hereditary PCT (Class I) in Italy and has identified a group of PCT patients with elevated URO-D activity who deserve further investigation.
|Issue number||11 PART II|
|Publication status||Published - 2000|
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