Phenylketonuria in Turkey, Ireland and west Scotland.

Abstract

The incidence of phenylketonuria (McKusick 261600) in Turkey is the highest recorded in any country, 1 in 4370 live births (Ozalp et al 1990). These authors ascribe the high incidence of the disease, i.e. of homozygotes for the PKU gene, to the fact that consanguineous marriages are common in Turkey. Assuming that consanguineous marriages have been a long-standing custom in Turkey, the gene frequency can be calculated from the standard formula i = qF + q2(1 F ) where i is the incidence of PKU, q is the gene frequency and F is the population inbreeding coefficient (see, e.g., Crow 1986). Since i has the value 1/4370 or 0.000228 3 (Ozalp et al 1990) and F = 0.01049 (Tungbilek and Ulusoy, 1989), q can be calculated to be 0.0108. This is lower than the PKU gene frequency in Ireland and West Scotland (0.0135-0.0142; Woolf et al 1975); the coefficient of inbreeding is so low in Ireland and West Scotland that it could be ignored in calculating q) but is as high as or higher than that so far recorded in any other country. The high incidence of PKU in Turkey must be largely (about 51%) explained by the high frequency of the gene in the population as well as by consanguinity in the parents (which accounts for about 49% of the incidence). Since homozygotes rarely reproduce or have normal offspring, each homozygote results in the loss of nearly two PKU genes from the population pool; hence the gene frequency should fall rapidly all the more rapidly as a consequence of the high rate of consanguineous marriages. Consanguinity cannot replace these lost PKU genes, it can only affect the distribution of the total population pool of PKU genes between homozygotes and heterozygotes. So high a frequency of a gene so deleterious in the homozygote could be explained, in the case of Ireland and West Scotland, only by some advantage to the heterozygote (Woolf et al 1975; Woolf, 1976, 1978). It seems probable that this applies also to PKU in Turkey. In Ireland and West Scotland it was found that, though the average numbers of pregnancies in PKU and control families were equal, in PKU families fewer of the pregnancies ended in spontaneous abortion; thus a woman heterozygous for PKU would have, on average, 7.4% more live-born offspring than a woman not carrying the PKU gene and, hence, ignoring the small exponential component, would have 7.4% more descendants, half of whom would be heterozygotes for PKU. This increase in the proportion of heterozygotes in the population, and therefore in the frequency of the PKU gene, would more than replace the PKU genes lost in homozygotes. It appears that the mother's heterozygosity protected the fetus against some hazard in the Irish and West Scottish environment; it would be interesting to discover whether the fetus was similarly protected in Turkey.