Hemophilia is a rare bleeding disorder, manifested by the inability of the blood to clot. The disease occurs due to alterations in genes that regulate our body to stop bleeding. Hemophila A and B are most common. It is caused by alterations or mutations in F8 or F9 genes respectively on X- chromosomes. The genes associated with hemophilia A and B, F8 and F9, respectively, provide instructions for producing clotting factors VIII and IX. Mutations in these genes result in reduced or non-functional clotting factors, leading to bleeding disorders. The severity of hemophilia in affected individuals can vary, depending on the specific mutation and the level of clotting factor present in their blood. Hemophilia C, caused by a deficiency in factor XI located on an autosome, however, is rare.
Dr Dipanjana Datta, BGCI Level II certified Genetic Counselor at Renew Healthcare, Hemophilia A/ B is an X-linked recessive genetic disorder. This means that the affected gene responsible for hemophilia is located on the X chromosome. Since males have one X and one Y chromosome (XY), and females have two X chromosomes (XX), haemophilia primarily affects males. Females can be carriers of the haemophilia gene if they inherit one normal X chromosome and one with a mutation, but they usually do not show symptoms themselves.
Though, haemophilia A/B have treatment in the form of supplementation of factor and gene therapy, however, males affected with hemophilia suffer from various co-morbidities including joint pain, bone-related issues, swelling, internal bleeds apart from excessive bleeding even in minor injury. Undiagnosed in case of mild haemophilia, surgery or an accident can cause death. Thus, diagnosis of the disease is of utmost importance.
Affected individuals are diagnosed through biochemical testing of the factors. Genetic testing can confirm the diagnosis of haemophilia and help in understanding the specific type and severity of the condition. A carrier female will have normal factor levels in most cases. Thus, female family members may choose to undergo carrier testing by genetic studies to determine if they carry a mutation in the F8 or F9 gene, which could be passed on to their children. Biochemical testing is not a suitable method as biochemistry might be normal.
Genetic testing involves analyzing a person's DNA to identify mutations in the F8 or F9 genes from blood or buccal swabs. In cases where there is a family history of haemophilia, invasive diagnostic methods like Chorionic Villi Sampling and amniocentesis followed by specific targeted genetic testing around 11 weeks ( about 3 months ) of pregnancy, can help determine the status of the fetus. This can help families make informed decisions about the pregnancy and prepare for the care of a child with haemophilia. Alternatively, Preimplantation genetic testing can be performed by taking a biopsy of the embryos formed by IVF on 5 th day and screening for the targeted mutation. This process is called PGT (M), which can help to identify healthy embryos without the trauma of repeated abortions after prenatal diagnosis.
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