[Genetic questions of hemophilia]

Haemophilia A and B are X-chromosomally recessively inherited. In the GDR the frequency of these genuine haemophilias is 1 to 6,500 male births. The frequency of sporadic haemophilias is still in dispute and certainly depends on the intensity of genealogic examinations. The mutation rate for haemophilia A is estimated to 1.3 to 3.6 x 10(-5). In secure female conductors the lyonisation evokes a considerable dispersion of the factor VIII coagulation activity, wherefore this is able to prove also only a small proportion, about 20-50%. The lyonisation apparently takes place in a critical anlage of less than 32 cells. Bleeding female conductors are in the first place the sequel of extreme lyonisation, more infrequently homozygotes or such ones with anomalies of the X-chromosomes. The state of female conductors is best characterized by th discrepancy between decreased factor VIII coagulation activity and the normal factor VIII associated antigen. At present numerous variants of this female conductor test are used, particularly concerning its calculatory evaluation. In many places only quotients from the two parameters are formed. Discriminancy-analytical methods brings without doubt better results. They allow to coordinate a certain probability to each result, which with the help of genealogic criteria may be combined to an evidence. Immunochemical determinations of the factor IX are certainly not of value for the proof of the state of female conductors of haemophilia B. The prenatal diagnostics of sex is recommended for pregnant conductors by amniocentesis in the 14th week of pregnancy. Only in few countries the prenatal diagnostics of haemophilia is possible. In blood tests taken by means of fetoscopy beginning with the 18th week of pregnancy the factor VIII coagulation property is determined by immunoradiometrical methods or recently even by means of a coagulation method. Though for the genetic consultation only female conductors in the reproductive phase are of importance, for the search of female conductors the whole lineage must be worked up genealogically, at least over four generations and with the help of archives material. The genetic consultation of haemophils and female conductors should be performed early and directedly, for important reasons also repeatedly.