Hum Genet (1982) 60:391-392

© Springer-Verlag 1982

Letter to the Editors

Incidence of Hunter's Syndrome I. D. Young and P. S. Harper University of Wales, Welsh National School of Medicine, Department of Medicine, Heath Park, Cardiff CF4 4XN, England

We were fascinated to read the report of Drs. Schaap and Bach (1980) suggesting that Hunter's syndrome may be a "Jewish disease". A survey of Hunter's syndrome patients throughout the United Kingdom conducted by ourselves, confirms that the incidence of 1 in 67,500 obtained by Drs. Schaap and Bach is indeed very high. As shown in Fig. 1, the patients were evenly distributed throughout the United Kingdom with no evidence of geographical clustering. The diagnosis was confirmed either enzymatically (Archer et al. 1981) or genetically (undisputed Xlinked pedigree) in 66 of the 88 patients ascertained: in the remaining 22 the diagnosis was regarded as probable based on clinical observations and the pattern of mucopolysacchariduria. The full results of this study have been presented (Young 1981). The results indicate that the overall incidence of Hunter's syndrome in the United Kingdom was approximately 1 in 132,000 male live births during the years of maximum ascertainment (1955-1974). We recognise two forms of the disorder, mild and severe. The incidence of the latter was 3.38 times that of the former. Although some 600 paediatricians and geneticists throughout the United Kingdom were approached, it is certainly possible that the incidence figures we have derived are underestimates. However we would be very surprised if the patients we have ascertained represent less than 50% of all known cases in the United Kingdom, since we recewed wide-spread cooperation from centres known to have special expertise and interest in the mucopolysaccharidoses. We observed no particular increased incidence amongst the British Jewish community, although the ethnic origins of some patients were unknown. Thus we conclude that the remarkably high incidence observed by Drs. Schaap and Bach is indeed worthy of note. Their intriguing suggestion that it may be due to a previous shift in the sex ratio in favour of increased heterozygous females as opposed to hemizygous males, with subsequent increase in affected males due to contemporary disregard of the Jewish purity laws, could be easily tested by studying the menstrual cycle in Hunter heterozygotes. If such an explanation is valid then these ladies should have relatively short follicular phases of the menstrual cycle with ovulation occurring on approximately the 12th day, i.e. the day when marital relations would be resumed by those who practice ritual separation. It is difficult to imagine a physiological basis for such a ]phenomenon. Other possible explanations for this high incidence in Israeli Jews might include admixture of autosomal recessive cases.

Neufeld et al. (1977) have reported two families showing autosomal recessive inheritance of Hunter's syndrome, and it may be pertinent that one of these families was Jewish. However the high incidence in Ashkenazi, Oriental, and Sephardic Jews cannot be readily explained by a single founder effect, so that other explanations may be sought. Perhaps the observed high incidence in Israel is in part a reflection of the high standard of medical care available in that country with referral of all suspected cases to a central diagnostic unit.

Offprint requests to: I. D. Young

Fig. 1

Place of residence of study patients

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392 References Archer IM, Harper PS, Wusteman FS (1981) An improved assay for iduronate 2-sulphate sulphatase in serum and its use in the detection of carriers of the Hunter syndrome. Clin Chim Acta 112:10%112 Neufeld EF, Liebars I, Epstein C J, Yatziv S, Milunsky A, Migeon BR (1977) The Hunter syndrome in females: is there an autosomal recessive form of iduronate sulfatase deficiency? Am J Hum Genet 29: 455-461

Schaap T, Bach G (1980) Incidence of mucopolysaccharidoses in Israel: is Hunter disease a "Jewish disease"? Hum Genet 56:221-223 Young ID (1981) A clinical and genetic study of Hunter's syndrome. A thesis submitted to the University of London for the degree of Doctor of Medicine

Received October 1, !981 / Revised February 12, 1982