Genetic diseases are generally caused by abnormality in the individual's genetic makeup or genome. The effect of this abnormality ranges from mild to severe. Those effects depend on the affected genetic components. The changes or abnormalities could be a mutation in a single base to that which could affects the large chromosome. The main forms of occurence are either through inheritance or spontaneous mutations. The basic types of inheritance are; single gene inheritance, multifactoral inheritance, chromosome abnormalities and mitochondrial inheritance. Haemophilia A is a type of chromosomal abnormality associated with a defective X chromosome hence tagged as X-linked disorder.
Haemophilia A
Haemophilia A is a genetic disorder that has been studied for several years. It is a congenital bleeding disorder that is X-linked as regards to its mode of inheritance. It is a condition that is associated with blood clotting factors VIII. The condition though considered being rare in occurrence, it affects about 6000 people within the United Kingdom populace (Bayer Healthcare, 2011).
There are two major types of blood disorders considered to be haemophilias. These are the haemophilia A and haemophilia B. The percentages of prevalence of the disorders are found to be 85% and 15% respectively for both A & B types. There is also haemophilia C. The categorizations as regards to the severity could be classified as mild, moderate or severe. The condition tends to affects males more compared to the females because of the pattern of inheritance which make males at risk of inheriting and expressing the disorder.
The only females that are likely to be affected by the clothing factors are those that are homozygous females (females that have inherited the traits from both affected father and carrier mother). The most affected people are those that are in the developing world who remain undiagnosed and untreated (Brian & Claudia, 2005). As a result of this factor, the life expectancy for both group of haemophiliacs are not comparable because of the fact that life expectancy for those living in the developed world are close to that of normal healthy individuals.
The overall overview of the problems that are associated with haemophilia is that the patient’s blood does not have enough of the implicated clotting factor hence leading the impaired clotting function. Anytime bleeding occurs it may end slowly than normal or may not even stop at all in some situations. Internal bleeding is still the most dangerous effects of haemophilia and if this is left untreated, it can cause deformities in the patient and in some cases death.
Symptoms and treatments
There are several signs and symptoms that are associated with haemophilia A. The most common ones include; bruises on stomach of a crawling baby. Those bruises could also be seen on the chest, buttock and back of the affected child. In some situations, the baby might not want to walk or crawl. The other commonest symptoms are the nose bleeding for longer periods, prolonged and excessive bleeding resulting from biting of lips or tongue. Bleeding that result from extraction sockets after tooth extraction or excessive bleeding post surgical procedures. Sometimes blood in the patient’s urine could also be some of the effects of the condition
Since there is a disruption in the coagulation cascade, spontaneous bleeding remains the order of the day. Any little trauma tends to be associated with excessive haemorrhage and there is recurrent spontaneous bleeding. The commonly affected sites include; "knee, elbow, muscles, central nervous system, gastrointestinal system, genitourinary system, pulmonary system and cardiovascular system (Zaiden, 2011)". Intracranial haemorrhage has been found to be common in younger patients that are less than 18 years of age (Zaiden, 2011). Affected females may show signs of heavy menstrual flow as a sign of being a carrier of haemophilia A.
The diagram above shows some of the forms of bleeding seen in affected children with haemophilia A.
Treatments
The use of intravenous recombinants or plasma that is concentrated with factor VIII is the most common form of therapies in case of haemophilia A. This is usually given in form of supplements. In cases of planned surgical procedure, the concentrate will have to be given prior to the surgery and post surgical procedures. There is ongoing research as regards to gene therapies that could help haemophilia A patients. Patient’s education and evaluation is a key to effective management of the condition. Patients need to be informed about the available therapies, risk factors, how to manage those risk factors so as to prevent some of the symptoms.
Genetic overview
Genetic perspective of haemophilia A is related to recessive inheritance of X-linked traits. The implication of this is that of the cause being only associated with the chromosome X. The meaning of this is that the gene that is responsible for the inheritance is on one of the arms of the X chromosome (long arm). Haemophilia A is related to the gene of FVIII that is located on Xq28 region (Zaiden, 2011) which comprises of 26 exons and 25 introns and about 2332 amino acids especially in the mature forms of FVIII (Zaiden, 2011). The issue is that there is lowered production of the FVIII which makes the coagulation cascade to be disrupted.
As a boy, inheriting the X chromosomes that are associated with haemophilia gene, the boy will definitely become haemophilic while this is not the case of female because of mode of inheritance in female which is related inheritance of XY chromosomes. A male always have XX chromosomes that double the chances of having the symptoms of the condition while females have 50 percent chance of passing the condition to her baby and also showing the symptoms. In most situations, because of the way inheritance do occur, females are generally carriers while males tend to show more effects of the diseases.
The diagram below shows the mode of inheritance of haemophilia A. The diagram shows the genotype and phenotypes of those children that are born by a carrier mother and a normal father. The implication of this is that a male with a single X chromosome that is inherited from the mother is going to be affected while that which inherited the X chromosome from the normal father will be normal.
Females are not usually affected hence they are usually carriers making them to have the genotype that show them as a carrier (an XX genotype with the implication of making one of the X chromosome being normal and other being affected). The phenotype in case of female is not expressive hence they are just carriers. In cases of males, their phenotype could either be expressive making them to be affected or not expressive because of the mode of inheritance which shows an XY chromosomal inheritance.
The mode of inheritance is the major reason for the prevalence and distribution of haemophilia A. The second major factor is the problem with diagnosis. This is because undiagnosed states usually make it more dangerous and easily transferable to the offspring. In cases whereby effective diagnosis has been made on time and treatment instituted, the chance of affected male marrying carrier females will be reduced hence helping to lower the chance of inheritance by the potential offspring.
The diagram above shows the pedigree of the genotypes of children from affected father and normal mother
The implication of the union between the affected father and normal mother is that among four children, two will be carriers, nil affected children and there will be two normal children. Boys from the family will be normal while the girls will be carriers hence reducing rate of effects but increasing the rate of carriers.
Summary
Haemophilia A is a condition that leads to disruption in production of clotting factor VIII. Consequences are related to spontaneous bleeding or haemorrhage from post-trauma experience. Males are more affected compared to females. Their phenotypes and genotype contributes to their risk of affectation. Female are usually carriers except some rare cases. Mode of genetic inheritance, phenotypic expression and genotype all plays important roles in pathophysiology of the condition. Patient education and provision of prophylaxis in form of factor VIII concentrate helps to reduce the associated consequences.
References
Bayer Healthcare, (2011). Haemophilia. Factor fitness teachers zone.
Retrieved, 20 March, 2012 from http://www.factorfitness.co.uk/PDF/Factor_Fitness-Teachers_Zone.pdf
Brian, M. & Claudia, B. (2005). Expanding haemophilia care in developing countries.
Retrieved, 20 March, 2012 from http://haemophilia.ie/PDF/Expanding%20Haemophilia%20Care%20in%20Developing%20Countries.pdf
Haemophilia Society, (2012). Haemophilia. Haemato-oncology.
Retrieved, 20 March, 2012 from http://www.kairos2.com/67_Haemophilia.pdf
Zaiden, R (2011). Haemophilia A. Medscape reference.
Retrieved, 20 March, 2012 from http://emedicine.medscape.com/article/779322-overview#aw2aab6b2b6aa
