VÝZNAM A PREVALENCE MUTACE C282Y GENUPRIMÁRNÍ HEMOCHROMATÓZY (HFE) V PATOGENEZIPOZDNÍ KOŽNÍ PORFYRIE (PCT)

Significance and Prevalence of the Primary Haemochromatosis C282YGene Mutation (HFE) in Pathogenesis of Porphyria Cutanea Tarda

Background.
Hitherto studies on the ethiopathogenesis of porphyria cutanea tarda (PCT) show that the majorpathogenic factor is iron ion, which acts via inhibition of the uroporphyrinogen decarboxylase. New speculationshave appeared on the possible relation of this role of iron and the occurrence of mutation of the recently discoveredgene of the hereditary hemochromatosis HFE, which may cause the iron overloading of the organism. Our paper describesprevalence of the C282Y gene mutation (HFE) together with the clinical and laboratory record in PCT patients.Methods and Results. PCT was diagnosed mostly on the basis of clinical finding of actinic-traumatic vesiculardermatitis and the typical laboratory record of elevated higher-carboxylic porphyrines in urine and stool. Otherlaboratory methods tested the liver functions, plasma iron level and its binding capacity, ferritine level. All patientunderwent routine haematological testing. Presence of antibodies against hepatitis C was also assayed (Elisa test2nd generation, Sanofi Pasteur). In patients with prominent laboratory alterations showing possibility of the hepaticstructural lesion, histology from the liver punctate was done. Frequency data of the C282Y gene mutation (HFE) inPCT patients was estimated on the basis of the genetic testing using PCR reaction of our own system. Group of PCTpatients had 69 persons (63 patients with the sporadic form and 6 patients with familiar form of the disease). Hereditaryhaemochromatosis C282Y gene mutation (HH) was found in 15 patients, three of them were homozygotes and twelveheterozygotes (three heterozygotes had the familiar form of the disease). Nobody in this group was positive in theHIV antibody testing. In all porphyria patients with the presence of mutated gene who underwent liver biopsy,siderosis of different degrees was identified. In three patients neither the phenotypic observation nor the laboratorytesting have shown haemochromatosis. Prevalence of C282Y gene mutation HFE in patients with porphyria cutaneatarda was studied. Such mutation was found in 15 persons (12 heterozygotes and 3 homozygotes) from the group of69 tested patients (21.7 %). Such frequency is significantly higher than in the control - nonporphyric - persons (10%). Patients were without clinical symptoms. Laboratory haematological changes, typical for HH, manifested insome of them only (elevated level of ferritine was found in 10 from 15 porphyria patients, elevated sideremia in oneof them). Red blood cell counts were in both homo- and heterozygotes normal. Concurrence of the two porphyrino-genic factors - presence of gene mutation HFE and hepatitis C infection - was not proved. Antibodies against hepatitisC virus were not identified in any of the patients. Siderosis was found to be only a symptomatic sign, which waspronounced in different degree in all 9 porphyria patients with C282Y gene mutation who underwent liver biopsy.Conclusions. Frequency of C282Y gene mutation in our patients with porphyria cutanea tarda appears similar tothat in other Middle European countries. It differs significantly from the frequency found in South European andNorth European countries (British).

Key words:
porphyria cutanea tarda, PCT, haemochromatosis, HFE gene, hepatic siderosis.