Morvay M, Koszo F, Dobozy A
Porphyrin Laboratory, Department of Dermatology and Allergology, Albert Szent-Györgyi Medical and Pharmaceutical Centre, Faculty of Medicine, University of Szeged, Szeged, Hungary
Porphyria cutanea tarda (PCT) results from a decreased activity of uroporphyrinogen decarboxylase in the liver. PCT is not a single monogenic disorder with a simple pattern of inheritance. Clinically overt form of any subgroup of PCT is induced by some liver damage caused by a long-term action of hepatotoxic agents like alcohol, estrogen, hepatitis (mainly type C), iron overload of any origin (e.g. hereditary haemochromatosis gene /HFE/ mutations) (1, 2). The goal of the study was to investigate the influence of the mutations H63D and C282Y in HFE gene on the porphyrin levels. PCT patients with and without HFE mutation(s) were examined; all they are registered and cared at our Department. Porphyrins were analysed with HPLC method of Seubert and Seubert (3). HFE mutations were identified by Zs. Nagy et al. (4). Mean values of the urinary porphyrin levels in untreated PCT patients are shown in the Table. In PCT, HFE gene mutation(s) can further increase the total porphyrin levels. Any heterozygous HFE gene mutation can cause only a slight alteration in the porphyrin pattern. In the case of either double heterozygosity (C282Y/H63D) or homozygosity for C282Y, perceptibly increased total porphyrin levels with higher share of the heptacarboxyl porphyrin fraction could be observed.
| HFE negative n=20 |
C282Y homo-zygous n=2 |
C282 hetero-zygous n=2 |
H63D hetero-zygous n=4 |
C282Y/H63D double heterozygous n=1 |
Healthy controls n=20 |
|
| Total porphyrin μmol/day |
4340 | 7159 | 4854 | 4112 | 4928 | <240 |
| Uro % Hepta % Hexa % Penta % Copro % |
66 22 4 3 5 |
54 28 6 6 6 |
65 23 3 4 5 |
68 20 4 3 4 |
52 28 8 5 7 |
<15 <5 <5 <5 >75 |
Different mechanisms take part in the deterioration of the decarboxylation. Complex contribution of all the possible simultaneous risk-factors may slightly alter the kinetics of the decarboxylation.
(1) Elder GH: Semin. Liv. Dis., 1998, 18, 67-75, (2) Roberts AG, et al.: Lancet, 1997, 349, 321-323, (3) Seubert S und Seubert A: Merck Spectrum, 1989, 2, 8-9, (4) Nagy Zs, et al.: Orv. Hetil., 2000, 141, 2031-2034. [Supported by: ETT 390/2003].