De Verneuil et al. (1978) classified porphyria cutanea tarda (PCT), the most common type of porphyria, into 2 types: type I, or 'sporadic' type, associated with approximately 50% level of uroporphyrinogen decarboxylase (UROD; 613521) in liver (Elder et ... De Verneuil et al. (1978) classified porphyria cutanea tarda (PCT), the most common type of porphyria, into 2 types: type I, or 'sporadic' type, associated with approximately 50% level of uroporphyrinogen decarboxylase (UROD; 613521) in liver (Elder et al., 1978; Felsher et al., 1982), and type II, or 'familial' type (176100), characterized by 50% deficient activity of the same enzyme in many tissues (Kushner et al., 1976; Elder et al., 1980). Type I is the most common form of PCT, comprising 70 to 80% of cases. The causes of the deficiency are often unclear and are probably multifactorial (review by Lambrecht et al., 2007).
Among 10 families containing 17 patients with PCT, Roberts et al. (1988) found that 4 were of type I. Each of these 4 families contained at least 2 subjects with overt PCT; all members of these families, including ... Among 10 families containing 17 patients with PCT, Roberts et al. (1988) found that 4 were of type I. Each of these 4 families contained at least 2 subjects with overt PCT; all members of these families, including 7 patients with overt PCT, had normal red cell uroporphyrinogen decarboxylase immunoreactive concentrations and enzyme activities. The patients were otherwise clinically and biochemically indistinguishable. The second group of 6 families (type II) showed decreased erythrocyte uroporphyrinogen decarboxylase segregating as an autosomal dominant trait. Recognized exacerbating factors of PCT include iron overload, excessive use of alcohol, exposure to polyhalogenated aromatic chemicals, exposure to estrogens, chronic viral hepatitis C, HIV infections, and mutation in the HFE gene (613609) that are responsible for hereditary hemochromatosis (235200) (review by Lambrecht et al., 2007).
Roberts et al. (1997) analyzed 41 patients with sporadic PCT and 101 controls for the presence of the C282Y (613609.0001) and H63D (613609.0002) mutations in the HFE gene and identified the C282Y mutation in 18 (44%) patients compared ... Roberts et al. (1997) analyzed 41 patients with sporadic PCT and 101 controls for the presence of the C282Y (613609.0001) and H63D (613609.0002) mutations in the HFE gene and identified the C282Y mutation in 18 (44%) patients compared to 11 (11%) controls (relative risk = 6.2; p = 0.00003). Seven patients were homozygotes; age at presentation was the same for those with or without the C282Y mutation. In 12 patients, the C282Y mutation was associated with markers of the HLA-A3-containing ancestral hemochromatosis haplotype. There was no difference in the frequency of the H63D mutation between the 2 groups. Roberts et al. (1997) concluded that inheritance of one or more hemochromatosis genes is an important susceptibility factor for sporadic PCT. Brady et al. (2000) investigated the relationship between age of onset of skin lesions and mutations (C282Y, 613609.0001; H63D, 613609.0002) in the hemochromatosis gene in 19 familial and 65 sporadic porphyria cutanea tarda patients. Familial porphyria cutanea tarda was identified by mutation analysis of the uroporphyrinogen decarboxylase gene. Five previously described and 8 novel mutations were identified. Homozygosity for the C282Y hemochromatosis mutation was associated with an earlier onset of skin lesions in both familial and sporadic porphyria cutanea tarda, the effect being more marked in familial porphyria cutanea tarda where anticipation was demonstrated in family studies. Analysis of the frequencies of hemochromatosis genotypes in each type of porphyria cutanea tarda indicated that C282Y homozygosity is an important susceptibility factor in both types but suggested that heterozygosity for this mutation has much less effect on the development of the disease. Dereure et al. (2001) evaluated 36 consecutive patients with either sporadic or familial PCT for the presence of the 3 main mutations of the HFE gene and identification of the transferrin receptor alleles. Seven patients (19%) showed heterozygous C282Y (613609.0001) mutation, but no C282Y homozygote was present; 5 patients (14%) carried homozygous H63D (613609.0002) mutation, while 8 (22%) were heterozygous for this mutation. One patient was heterozygous for the S65C (613609.0003) mutation (3%). Iron parameters demonstrated overload in all patients, without a clear difference between patients with and without deleterious mutations of the HFE gene. Infection by hepatitis C virus was documented in 20 patients (56%), and was significantly less frequent in patients with deleterious HFE mutations. The profile of transferrin receptor alleles in PCT patients did not show significant variation compared with the general population. Dereure et al. (2001) concluded that there is a high frequency of HFE mutations in patients with PCT and that HFE gene abnormalities might play a significant part in the PCT pathomechanism, probably through iron overload; by contrast, transferrin receptor polymorphisms do not appear to play a significant part in iron overload in PCT.
The incidence of PCT varies from approximately 1 in 25,000 in the United States to approximately 1 in 5,000 in the Czech Republic and Slovakia. Type I PCT is more commonly seen in males (review by Lambrecht et ... The incidence of PCT varies from approximately 1 in 25,000 in the United States to approximately 1 in 5,000 in the Czech Republic and Slovakia. Type I PCT is more commonly seen in males (review by Lambrecht et al., 2007).