ALT, alanine aminotransaminase.
Iron status and HFE mutations in first-degree relatives of patients with sporadic porphyria cutanea tarda, in a Mediterranean area
Version of Record online: 14 MAR 2005
Journal of Internal Medicine
Volume 257, Issue 4, pages 389–390, April 2005
How to Cite
García-Morillo, J. S., Ramírez Lorca, R., Bernabeu-Wittel, M., Stiefel García-Junco, P., Pamies Andreu, E. and Carneado de la Fuente, J. (2005), Iron status and HFE mutations in first-degree relatives of patients with sporadic porphyria cutanea tarda, in a Mediterranean area. Journal of Internal Medicine, 257: 389–390. doi: 10.1111/j.1365-2796.2005.01462.x
- Issue online: 14 MAR 2005
- Version of Record online: 14 MAR 2005
We read with interest the manuscript of Harper et al. , that analysed the presence of mutations of the haemochromatosis-associated gene (HFE) in patients of northern Europe with sporadic porphyria cutanea tarda (sPCT); the authors found that the presence of C282Y mutation of HFE was associated to iron overload and overt haemochromatosis. Nevertheless, it is already known that the polymorphism distribution of HFE may differ in different populations; in fact, the H63D and less S65C mutations are closely related to iron overload in patients with sPCT in Mediterranean areas. In Spain the specific HFE mutation associated to sPCT is H63D [2–4]. We were interested in the early detection of these HFE mutations in first-degree relatives of patients with sPCT, in order to identify those who could be susceptible, after hypothetical exposure to triggering factors like alcohol, oestrogens or liver viral infections , of developing overt PCT.
For this purpose we determined the three major HFE mutations (C282Y, H63D and S65C), porphyrins (uro-III and hepta-III) in a 24-h urine sample, as well as the iron load status in 25 first-degree relatives (16 were offspring, seven sibblings, and two parents) of 11 unrelated patients with sPCT. HFE mutations were analysed by polymerase chain reaction using RsaI, BclI, and HindI [6, 7].
The relatives were mainly women (n = 18); the mutation H63D was present in five (20%) of them, and two (8%) were heterozygous for the C282Y mutation. None of them showed elevated urine porphyrins, and iron metabolism alterations were also absent in those with different HFE mutations. A description of the HFE genotypes of the studied relatives is detailed in Table 1.
|Genotype||n (%)||Sex (M/F)||Ferritin (μg dL−1)||Saturation index (%)||Haemoglobin (g/L)||ALT (U/L)|
|C282Y/–||2 (8)||2/0||44.00 ± 26.87||31.45 ± 18.32||156.60 ± 24.68||19.30 ± 23.1|
|H63D/–||5 (20)||1/4||58.00 ± 59.02||29.50 ± 17.44||154.50 ± 21.93||22.25 ± 12.6|
|No mutations||18 (72)||4/14||94.22 ± 113.77||27.42 ± 7.54||133.4 ± 21.78||17.89 ± 7.2|
In our study, in contrast to results of Harper et al. , the mainly observed genotype was H63D mutation. However, the presence this mutation in relatives of patients with sPCT was not correlated with iron overload nor with altered liver function, so this issue, in our opinion, remains to be elucidated.
A second finding of our study that bears consideration is the high frequency of heterozygous H63D overexpression in women (male 1/female 4), similar to that described by other authors ; this finding, together with the expanded use of oestrogens and increase in alcohol consumption by women, could induce changes in the features of PCT in the future. In fact a 53% of the evaluated women were receiving oestrogens, and a 67% drank alcohol every day.
We agree with Harper et al. that determination of iron load status and HFE mutations in patients with sPCT and their first-degree relatives could be useful in the early detection and treatment of iron overload; nevertheless we recommend this last determination only in those persons with iron overload (by means of a saturation index >50%), or demonstrated liver function abnormalities. In any case we think that future studies are needed to definitively establish the role of H63D mutation in the development of PCT in relatives of patients with sPCT of Mediterranean areas.
Conflict of interest statement
No conflict of interest was declared.