Eur J Pediatr (2008) 167:703–706 manifestations [22, 23]. Thus, children with EPP are often labeled as hysterical, hypochondriac, or even malingering, a distressing situation for both the patients and their parents [2, 22]. To the best of our knowledge the complete absence of visible skin lesions in early childhood EPP has only been described once to date [12]. The symptoms in EPP are associated with an overpro- duction and accumulation of lipophilic protoporphyrin as a result of FECH deficiency [28]. Excess deposition of protoporphyrin in the skin leads to cutaneous photosensi- tivity upon UV light exposure with maximum susceptibility at a wavelength around 400 nm (Soret band) [22]. Upon excitation, protoporphyrin exerts its phototoxic effects through the generation of reactive oxygen species (ROS). ROS can induce lipid peroxidation, oxidation of amino acids, and mediator release from mast cells, contributing to the acute photosensitivity, and protein cross-linking leading to cell membrane damage and cell death [3, 7, 13, 17, 25]. The diagnosis of EPP is based on the clinical symptoms and verified by a significant increase of FEP (more than five times the normal level of 0 to 300 μg/l ) in peripheral erythrocytes [15, 18, 28]. Since protoporphyrin is a hydrophobic metabolite, it is not renally excreted. Hence, urinary porphyrin values are usually normal [15, 23]. Another diagnostic modality includes fluorescence micros- copy of erythrocytes [2, 17]. Histological changes are predominantly seen in the upper dermis and include deposition of amorphous material containing immunoglobulins, complement components, glycoproteins, acid glycosaminoglycans, and lipids around blood vessels [5, 21, 24, 26, 27, 29]. However, these alterations are not specific. Regardless of the aforemen- tioned finding, we emphasize that it is unnecessary to take a skin biopsy if one of the cutaneous porphyrias is suspected because of two reasons. Firstly, simple non-invasive biochemical laboratory techniques can easily prove or exclude the presumptive diagnosis of porphyria. Secondly, any kind of external trauma, such as a biopsy or excision, inevitably constitutes an unnecessary risk for delayed or disturbed wound healing in porphyria patients. The differential diagnoses of EPP include solar derma- titis, solar urticaria, polymorphous light eruption, lipoid proteinosis, hydroa vacciniforme, and lupus erythematosus [2, 22]. Elevated FEP levels can also be found in lead poisoning, anemia, renal failure, cholestasis, and liver failure. However, these conditions are not associated with photosensitivity [13, 18, 23]. Beside the cutaneous manifestations, the most important concern in EPP patients is the development of cholestasis with rapid accumulation of protoporphyrin in hepatobiliary structures resulting in severe liver damage and hepatic failure. Although rarely occurring, progressive liver failure is a well-recognized complication in EPP, and about one 705 third of EPP patients show biochemical liver abnormalities [6, 13]. Therefore, liver function tests should be performed annually [13, 28]. In our patient, no liver dysfunction has been detected so far. Although in rare instances an autosomal recessive inheritance pattern has been described, EPP is a predom- inantly autosomal dominantly transmitted disorder with incomplete penetrance resulting from mutations in the FECH gene on chromosome 18q21.3 [31, 32]. To date, more than 65 different FECH mutations have been reported, reflecting the genetic heterogeneity encountered in EPP [13, 28]. Recently, the genetic mechanisms underlying the cutaneous symptoms in EPP have been uncovered. It is clear now that only those individuals will develop skin symptoms who not only inherit a heterozy- gous FECH gene mutation on one parental allele, but also a specific intronic FECH polymorphism on the other parental allele [8]. Thus, clinically overt EPP results from a marked deficiency of FECH activity below a certain threshold due to co-inheritance of a specific FECH gene mutation with a low-penetrance IVS3-48C allele. Recent studies indicate that the frequency of the IVS3-48C allele shows a high degree of variability in different ethnic groups [9]. The identification of the molecular mechanisms underlying the manifestation of photosensitivity in EPP certainly has to be considered a milestone in porphyria research. Still, the development of protoporphyrin-induced hepatic disease and the molecular mechanisms governing the phenotype with severe liver injury are not well understood. It seems that other as yet unidentified factors may contribute to the pathogenesis of severe liver failure in EPP. The current treatment modalities for EPP are limited and not effective in all patients [13]. In an ideal scenario, the harmful effects of exposure to visible light should be prevented. This can partially be achieved with sunscreens containing titanium oxide or zinc oxide. Common sunscreens, even those with high UV absorption capacity, do not block visible light and, thus, have no protective effect [2, 28].Consequent avoidance of UV light exposure and sun protection by protective clothing remains the most important measure in preventing acute photosensitivity and was also advised to our patient [13, 14, 18, 28]. The effectiveness of other modalities such as antioxidants (e.g., beta-carotene), cysteine, narrow-band UVB-phototherapy, and oral antihistamines remains doubtful and is certainly not of benefit in all patients. In the future, gene therapy approaches might play a role in the treatment of EPP because, e.g., normal ferrochelatase activity could be restored in vitro by transferring a wild-type copy of the FECH gene into cultured fibroblasts of EPP patients [16]. In conclusion, the diagnosis of EPP is often delayed or missed. Therefore, EPP should always be considered in photosensitive children, especially when the subjective