After the establishment of NAPOS in 1999, the number of persons diagnosed with porphyrias in Norway increased from about 10 – 20 per year before 1999 to a maximum of 110 in 2004. The pre-1999 figures are uncertain, as they are based on information from different hospitals in Norway. The rarer diagnoses have also been made more frequently than previously. These increases are probably attributable to improved diagnostic methods, greater focus on and more knowledge about the porphyrias, and the effect of family studies.
Some of the new cases of variegate porphyria and hereditary coproporphyria resulted from changes in former porphyria diagnoses, following new biochemical and genetic studies. During the same period, a number of persons who had previously been diagnosed as having porphyria had their diagnosis «removed» because it proved to be based on incorrect interpretation of analytical results.
As the porphyrias are rare, there is little reliable data on prevalence. There may also be large differences in prevalence from population to population or across geographical areas, owing, inter alia, to founder effects.
Porphyria cutanea tarda is the most commonly occurring porphyria in the majority of populations (1). The prevalence in our study was similar to that reported from Sweden (10 : 100 000) (9), but higher than in the UK (4 : 100 000) (4). In most populations, the hereditary form of porphyria cutanea tarda accounts for about 25 % of cases (10) – (13). In our study we found a substantially larger percentage of hereditary cases (60 %). A study from 2009 (3) showed that 74 % of the hereditary cases of porphyria cutanea tarda in Norway are due to two frequently occurring mutations.
In most populations, acute intermittent porphyria is the most frequently occurring acute porphyria. Although the disease has autosomal dominant inheritance, clinical penetrance is low, and it is assumed that only 10 – 20 % of genetically predisposed individuals will ever develop symptomatic disease. A new study examining the incidence of acute intermittent porphyria in several European countries showed a calculated prevalence (estimated on the basis of incidence in countries participating in the study) of symptomatic acute intermittent porphyria of 0.5 : 100 000 (14), which is substantially lower than our estimate (4 : 100 000) and the estimate from Sweden (10 : 100 000, but this includes predictively identified non-symptomatic cases) (15, 16).
The high prevalence in Norway and Sweden is partly due to a founder mutation originating from Arjeplog in Northern Sweden, where the estimated prevalence is 2 000 : 100 000 (15). In Saltdal Municipality in Norway’s Nordland County, where this mutation also occurs frequently, the prevalence is estimated at 600 : 100 000 (7). An additional explanation may be that family screening is more easily available in Norway and Sweden, and more is known about the diseases, with the result that more patients are correctly diagnosed.
Few studies on diagnostic delay in the porphyrias have been conducted, but studies on erythropoietic protoporphyria in Sweden (17) and the UK (18) have reported 18 and 12 years’ delays respectively, compared with 17 years in our study. The disease is diagnostically challenging, not only because it is very rare, but also because the clinical presentation may be a small child who cries and is agitated when exposed to the sun, without this being accompanied by distinct skin lesions (1). This study includes too few patients with erythropoietic protoporphyria to allow us to investigate whether time to diagnosis is shorter now than in the past, but the studies from Sweden and the UK have failed to demonstrate any change (17, 18).
The amount of monitoring and follow-up needed for the different diagnoses is determined by both the type of porphyria and whether the patient has symptomatic disease or is genetically predisposed without having had symptoms. With most of the porphyrias, it is possible to prevent attacks or relapses. With correct treatment and follow-up, many patients may therefore remain free of symptoms for most of their lives, and complications such as hypertension, renal failure, hepatocellular carcinoma in patients with acute porphyrias (19, 20) and liver failure in erythropoietic protoporphyria (21) can be detected early.
Despite the fact that all patients who have had symptoms are advised to go for annual check-ups (22), over half of patients with symptomatic acute intermittent porphyria and a third of those with porphyria cutanea tarda report that they never do. In light of this information, NAPOS published detailed diagnosis-specific guidelines in 2010 for the monitoring and follow-up of porphyria patients (22).
In general, there is consistency between the symptoms reported by Norwegian patients in connection with attacks of acute intermittent porphyria and those observed in other studies (5, 23, 24). Acute attacks may be precipitated by a number of factors, such as hormonal changes (e.g. menstruation), unsafe drugs, alcohol, fasting/dieting, psychological and physical stress and other illnesses (4) – (6). The use of drugs (40 %) as a precipitating factor was reported more frequently in our study than in studies from Sweden (20 %) (5) and South Africa (10 %) (6). In addition, 18 % of the women in our study specifically reported contraceptive pills as a precipitating factor.
In particular, participants with acute intermittent porphyria and erythropoietic protoporphyria reported that they had a reduced quality of life as a result of their disease. These findings must be interpreted with caution, as they are not based on a validated method. A lower quality of life has previously been reported in patients with acute porphyrias compared to healthy individuals and diabetics (25).
Recent studies (17, 18) have shown that patients with erythropoietic protoporphyria have a severely reduced quality of life, which is partly explained by the long diagnostic delay, major restrictions on daily living and the fact that there are few treatment options. In light of the fact that several of the porphyrias may have long diagnostic delays, may cause severe and/or pronounced distress and are dependent on life-long follow-up, new studies are needed to assess the need for follow-up and help for porphyria patients at different stages of life.
The strength of the present study is that it provides a comprehensive overview of porphyrias in Norway, including all porphyria patients registered at NAPOS since its establishment in 1999. The study therefore encompasses many patients, despite the fact that it concerns such rare conditions. In addition, the response rate in the Norwegian Porphyria Registry is relatively high, at 70 %. Non-response analyses have not been conducted, but we see that the response rate is higher for women than for men, and also for patients with erythropoietic protoporphyria. However, it must be taken into consideration that the data included in the registry are patient-reported.
There is still little systematic knowledge of the natural history of the various porphyrias and of treatment efficacy. Many patients with a rare disease report challenging encounters with the healthcare system. The Norwegian Porphyria Registry will use the systematically acquired registry data to develop and implement guidelines that may improve the clinical management of the porphyrias. A joint European porphyria registry, to be managed by NAPOS, was established recently (26). This registry will be capable of encompassing larger numbers of porphyria patients, which will result in more reliable data and in turn a better foundation for evidence-based practice.