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2.3. Acute intermittent porphyria
2.3.1. History

The modern history of acute porphyrias, reviewed extensively elsewhere (Goldberg and Rimington 1962, Dean 1963, Tschudy et al. 1975), begins at the end of the 19th century, when an increasing number of patients with abdominal pain and neurological symptoms was described. The typical attacks of acute porphyria were associated already in these early days with drug treatment.

Most of the porphyrin nomenclature is based on Hans Fischer's, a Nobel laureate in 1930, studies on the heme biosynthesis in the 1920's. In 1937 Jan Waldenström, who had previously worked in Fischer's laboratory, described over one hundred patients with acute porphyria, most of whom originated from a small village in Northern Sweden (Waldenström 1937). In this study the Mendelian dominant mode of inheritance in AIP was demonstrated for the first time. Later, he proposed that porphyrias could result from enzyme defects in the heme pathway and was also the first to use the term 'acute intermittent porphyria' (Waldenström 1957). A screening test for porphobilinogen was introduced in 1941 by Watson, who also was Fischer's co-worker (Watson and Schwartz 1941). He also introduced hematin for treatment of acute porphyrias (Watson et al. 1978). In the 1960's Granick discovered that ALA synthase, the first step in heme biosynthesis, is induced by chemicals which cause acute porphyria (Granick 1963, Granick 1966). This observation led to the concept that overproduction of ALA may represent the primary genetic defect in all acute porphyrias (Granick 1966), but this hypothesis was soon found to be false because increased activity of this enzyme by itself could not account for the distinct patterns of porphyrin precursors and porphyrin excretion. The biochemical background of AIP was confirmed when it was demonstrated that the disease is due to a defect in PBGD (Miyagi 1970, Meyer et al. 1972).

The characterization of the porphobilinogen deaminase gene (Raich et al. 1986, Grandchamp et al. 1987, Chretien et al. 1988, Lee 1991a, Namba et al. 1991) initiated multiple investigations of the molecular genetic background of AIP, and today several mutations responsible for AIP have been identified (see chapter 2.5.2).

The first Finnish patient with acute porphyria was reported in 1928 (Langenskiöld 1928). The first comprehensive study of the prevalence and clinical characteristics of acute porphyrias in Finland was reported in 1976 by Pertti Mustajoki and Pentti Koskelo (Mustajoki and Koskelo 1976). The prognosis, precipitating factors and associated diseases in Finnish patients with acute porphyrias have been investigated thoroughly by Raili Kauppinen and Pertti Mustajoki (Kauppinen et al. 1992).

2.3.2. Prevalence

AIP is the most common type of acute porphyria in most countries (Kappas et al. 1995), only in the Republic of South Africa is the prevalence of variegate porphyria higher than that of AIP. The prevalence of AIP in Finland has been estimated to be 3:100000 (Mustajoki and Koskelo 1976). In other countries the reported prevalence figures are similar or slightly higher: 5-10:100000 in the United States of America, in Western Australia 3:100000 (Tschudy et al. 1975). The highest prevalence of AIP has been described in northern Sweden where the prevalence is 100:100000 and, furthermore, in two small municipalities the prevalence is as high as 0.5-2%. However, the overall prevalence of AIP in Sweden is only 10:100000 (Andersson 1997). In a study of healthy Finnish blood donors the prevalence of low PBGD activity was 1:500 (Mustajoki et al. 1992) and similar figures were obtained in a study which consisted of healthy French blood donors (Nordmann et al. 1997). This implies that the prevalence of AIP, though asymptomatic, may be much higher than previously estimated.