Symposium : Hematology/Oncology-I Indian J Pediatr 1998; 65 : 645-649 fl [I I I Prenatal Diagnosis of Haemophilia Renu Saxena, Sujata Mohanty and V.P. Choudhry Department of Haematology, All India Institute of Medical Sciences, New Delhi Abstract. Haemophilia A is a severe bleeding disorder caused by a deficiency in clotting factor v,,, (FVIII).Itis an X-linked recessive bleeding disorder affecting one in 10,000 males. Prevalence of the haemophilia gene in the general population has increased recently due to advances in treat- ment, which has resulted in reproductive fitness among heamophiliacs. Patients sufferingfrom this disease and their families are faced with problems relating to morbidity and mortality from the dis- ease. These include a continual risk of uncontrolled bleeding, haemarthroses and subsequent arthropathy and above all, the genetic risk to progeny. Factor VIII gene is very large with 26 exons. Defects in this gene result in the deficiency of FVIll molecule. With the advent of recent advances in the molecular biology, it is possible to identify the multiple molecular defects such as point mutations, premature stop codons, deletions, and inversions etc in the FVlII gene in patients with haemophilia. Nowadays the use of polymerase chain reaction (PCR)-based linkage analysis and direct mutation detection in the chorionic villus sample obtained at 10-12 weeks of gestation has significantly improved the prenatal diagnosis of haemophilia. (Indian J Pediatr 1998; 65 : 645-649) Key words : Haemophilia-A; Prenatal diagnosis; Polymerase chain reaction; Mutation; Restriction fragment lef~gthpolymorphism. Haemophilia A is the commonest coagula- tion disorder 1. It has been estimated that there are 51,204 haemophiliacs in our coun- try ~ and one new case of severe haemo- philia per 10,000 live male births is being added per year. With the current birth rate of 32 per 1000, and a male : female ratio of 1 : 1, this works out to 1300 new cases of haemophilia per year. Haemophilia A is caused by a number of mutations in the large, complex factor VIII (FVIII)'gene. This gene, which is 186 kb long, and contains 26 exons, encodes a protein Of 2351 amino acids with a relative Reprint requests : Renu Saxena, Department of Haematology, IRCH Building, All India Institute of Medical Sciences, Ansari Nagar, New Delhi - 110 029. molecular mass of 267,039 daltons. It is lo- cated on the long arm of X-chromosome, at a distance of about one megabase from the telomere 2. Factor VIII is a plasma glycoprotein which after post-translational modification plays an important role in the intrinsic coagulation pathway. Patients with haemophilia have a generalised bleeding tendency leading to high morbid- ity and mortality. Management requires administration of FVIII concentrates, cryoprecipitate or fresh frozen plasma. Average factor VIII concen- trates required to control bleeding episodes are nearly 3,84,030,000 units per year 1. Thus 51,204 hemophiliacs would require approximately 384 million units of FVIII annually in india to control the bleeding episodesL The current cost of FVIII being