"births for haemophilia B. About 18,000 people in the United States have haemophilia. Each year in the US, about 400 babies are born with the disorder. Haemophilia usually occurs in males and less often in females. It is estimated that about 2500 Canadians have haemophilia A, and about 500 Canadians have haemophilia B. The first medical professional to describe the disease was Abulcasis. In the tenth century he described families whose males died of bleeding after only minor traumas. While many other such descriptive and practical references to the disease appear throughout historical writings, scientific analysis did not begin until"
"of diseases most commonly phenotypically affect males and rarely females. Hemophilia, or haemophilia, is an X-linked recessive disorder that impairs the body's control over blood clotting. Haemophilia A and Haemophilia B arise from mutations in the genes for factor VIII and factor IX, respectively. Females with this disease are almost exclusively unaffected, obligate carriers. The mutations can be passed on to offspring by mothers and fathers, but the phenotype is only expressed in males that inherit the mutation. All daughters of a hemophiliac father are obligate carriers of the disease. In an autosomal recessive disease, if an individual is heterozygous"
"haemophiliac himself). Hence, haemophilia is expressed far more commonly among males than females, while double-X females are far more likely to be silent carriers, survive childhood and to submit each of her genetic children to an at least 50% risk of receiving the deficient gene. However, it is possible for female carriers to become mild haemophiliacs due to lyonisation (inactivation) of the X-chromosomes. Haemophiliac daughters are more common than they once were, as improved treatments for the disease have allowed more haemophiliac males to survive to adulthood and become parents. Adult females may experience menorrhagia (heavy periods) due to the"
"of gene therapy to treat haemophilia A. Two Dutch studies have followed haemophilia patients for a number of years. Both studies found that viral infections were common in haemophiliacs due to the frequent blood transfusions which put them at risk of acquiring blood borne infections, such as HIV, hepatitis B and hepatitis C. In the latest study which followed patients from 1992 to 2001, the male life expectancy was 59 years. If cases with known viral infections were excluded, the life expectancy was 72, close to that of the general population. 26% of the cases died from AIDS and 22%"
"cancel it out, so the deficient gene is not masked and the disorder will develop. Since a male receives his single X-chromosome from his mother, the son of a healthy female silently carrying the deficient gene will have a 50% chance of inheriting that gene from her and with it the disease; and if his mother is affected with haemophilia, he will have a 100% chance of being a haemophiliac. In contrast, for a female to inherit the disease, she must receive two deficient X-chromosomes, one from her mother and the other from her father (who must therefore be a"
"more common in cases of severe and moderate haemophilia. Complications may arise from the disease itself or from its treatment: Haemophilic arthropathy is characterized by chronic proliferative synovitis and cartilage destruction. If an intra-articular bleed is not drained early, it may cause apoptosis of chondrocytes and affect the synthesis of proteoglycans. The hypertrophied and fragile synovial lining while attempting to eliminate excessive blood may be more likely to easily rebleed, leading to a vicious cycle of hemarthrosis-synovitis-hemarthrosis. In addition, iron deposition in the synovium may induce an inflammatory response activating the immune system and stimulating angiogenesis, resulting in cartilage and"
"in consultation with a doctor. Like most aspects of the disorder, life expectancy varies with severity and adequate treatment. People with severe haemophilia who don't receive adequate, modern treatment have greatly shortened lifespans and often do not reach maturity. Prior to the 1960s when effective treatment became available, average life expectancy was only 11 years. By the 1980s the life span of the average haemophiliac receiving appropriate treatment was 50–60 years. Today with appropriate treatment, males with haemophilia typically have a near normal quality of life with an average lifespan approximately 10 years shorter than an unaffected male. Since the"
"Haemophilia C Haemophilia C (also known as plasma thromboplastin antecedent (PTA) deficiency or Rosenthal syndrome) is a mild form of haemophilia affecting both sexes, due to factor XI deficiency. However, it predominantly occurs in Jewish people of Ashkenazi descent. It is the fourth most common coagulation disorder after von Willebrand's disease and haemophilia A and B. In the United States, it is thought to affect 1 in 100,000 of the adult population, making it 10% as common as haemophilia A. In terms of the signs/symptoms of haemophilia C, unlike individuals with Haemophilia A and B, people affected by it are"
"Hereditary persistence of fetal hemoglobin Hereditary persistence of fetal hemoglobin (HPFH, BrE: ""Hereditary persistence of foetal haemoglobin"") is a benign condition in which significant fetal hemoglobin (hemoglobin F) production continues well into adulthood, disregarding the normal shutoff point after which only adult-type hemoglobin should be produced. The condition is usually asymptomatic, and is only noticed when screening for other hemoglobin disorders. This is usually caused by mutations in the ""β or α"" globin gene cluster, or the γ promoter gene region. The percentage of incorrect expression might be as low as 10-15% or as high as 100% of the total"
"offspring. A homozygous recessive individual has an abnormal phenotype and is guaranteed to pass the abnormal gene onto offspring. In the case of hemophilia, it is sex-linked thus only carried on the X chromosome. Only females can be a carrier in which the abnormality is not displayed. This woman has a normal phenotype, but runs a 50-50 chance, with an unaffected partner, of passing her abnormal gene on to her offspring. If she mated with a man with haemophilia (another carrier) there would be a 75% chance of passing on the gene. ""Genotyping"" is the process of elucidating the genotype"
"expectancy of the standard hemoglobin (HgbA) homozygote and also the heterozygote is normal (though heterozygote individuals will suffer periodic problems). The sickle-cell variant survives in the population because the heterozygote is resistant to malaria and the malarial parasite kills a huge number of people each year. This is balancing selection or genetic polymorphism, balanced between fierce selection against homozygous sickle-cell sufferers, and selection against the standard HgbA homozygotes by malaria. The heterozygote has a permanent advantage (a higher fitness) so long as malaria exists; and it has existed as a human parasite for a long time. Because the heterozygote survives,"
"1.5 in 100,000 people, corresponding to a current prevalence of about 8,000 in the EU, 5,000 in the U.S., and 2,000 in Japan. Patients who lack chronic heart failure and those who respond well to prednisone or a similar drug have a good prognosis. However, the mortality rate rises in patients with anaemia, chromosomal abnormalities or a very high white blood cell count. Hypereosinophilic syndrome The hypereosinophilic syndrome (HES) is a disease characterized by a persistently elevated eosinophil count (≥ 1500 eosinophils/mm³) in the blood for at least six months without any recognizable cause, with involvement of either the heart,"
"Hypereosinophilic syndrome The hypereosinophilic syndrome (HES) is a disease characterized by a persistently elevated eosinophil count (≥ 1500 eosinophils/mm³) in the blood for at least six months without any recognizable cause, with involvement of either the heart, nervous system, or bone marrow. HES is a diagnosis of exclusion, after clonal eosinophilia (such as ""FIP1L1-PDGFRA""-fusion induced hypereosinophelia and leukemia) and reactive eosinophilia (in response to infection, autoimmune disease, atopy, hypoadrenalism, tropical eosinophilia, or cancer) have been ruled out. There are some associations with chronic eosinophilic leukemia as it shows similar characteristics and genetic defects. If left untreated, HES is progressive and"
"to their children than carrier females, though all daughters they sire will be carriers and all sons they father will not have haemophilia (unless the mother is a carrier). There are numerous different mutations which cause each type of haemophilia. Due to differences in changes to the genes involved, people with haemophilia often have some level of active clotting factor. Individuals with less than 1% active factor are classified as having severe haemophilia, those with 1-5% active factor have moderate haemophilia, and those with mild haemophilia have between 5-40% of normal levels of active clotting factor. Haemophilia can be diagnosed"
"This is mainly due to excess mortality from cirrhosis and liver cancer. Patients who were treated with phlebotomy lived longer than those who weren't. Patients without liver disease or diabetes had similar survival rate to the general population. Haemochromatosis is one of the most common heritable genetic conditions in people of northern European extraction with a prevalence of 1 in 200. The disease has a variable penetration and about 1 in 10 people of this demographic carry a mutation in one of the genes regulating iron metabolism, the most common allele being the C282Y allele in the ""HFE"" gene. The"
"""hereditary haemochromatosis"". Hereditary haemochromatosis is an autosomal recessive disorder with estimated prevalence in the population of 1 in 200 among patients with European ancestry, with lower incidence in other ethnic groups. The gene responsible for hereditary haemochromatosis (known as HFE gene) is located on chromosome 6; the majority of hereditary haemochromatosis patients have mutations in this HFE gene. Hereditary haemochromatosis is characterized by an accelerated rate of intestinal iron absorption and progressive iron deposition in various tissues. This typically begins to be expressed in the third to fifth decades of life, but may occur in children. The most common presentation"
"Homocysteine permanently degrades cysteine disulfide bridges and lysine amino acid residues in proteins, gradually affecting function and structure. Simply put, homocysteine is a 'corrosive' of long-living proteins, i.e. collagen or elastin, or lifelong proteins, i.e. fibrillin. These long-term effects are difficult to establish in clinical trials focusing on groups with existing artery decline. Klippel–Trenaunay syndrome and Parkes–Weber syndrome are relevant for differential diagnosis. Another cause is chronic alcohol consumption due to the vasodilatation side effect in relation to gravity and blood viscosity. Treatment can be either conservative or active. Active treatments can be divided into surgical and non-surgical treatments. Newer"
"the meningeal inflammation in an attempt to reduce risk of mortality and reduce the possibility of brain damage. Survivors of ""Haemophilus"" meningitis may experience permanent damage caused by inflammation around the brain, mostly involving neurological disorders. Long-term complications include brain damage, hearing loss, and mental disability. Other possible long-term effects are reduced IQ, cerebral palsy, and the development of seizures. Children that survive the disease are more often held back in school, and are more likely to require special education services. Negative long-term effects are more likely in subjects whose treatments were delayed, as well as in subjects who were"
"Hemophagocytic lymphohistiocytosis Hemophagocytic lymphohistiocytosis (HLH), also known as haemophagocytic lymphohistiocytosis (British spelling), and hemophagocytic or haemophagocytic syndrome, is an uncommon hematologic disorder seen more often in children than in adults. It is a life-threatening disease of severe hyperinflammation caused by uncontrolled proliferation of activated lymphocytes and macrophages, characterised by proliferation of morphologically benign lymphocytes and macrophages that secrete high amounts of inflammatory cytokines. It is classified as one of the cytokine storm syndromes. Primary HLH, also known as familial haemophagocytic lymphohistiocytosis (FHL) or familial erythrophagocytic lymphohistiocytosis, is a heterogeneous autosomal recessive disorder found to be more prevalent with parental consanguinity."
"of sickle cell anemia in humans, a hereditary disease that damages red blood cells. Sickle cell anemia is caused by the inheritance of an allele (HgbS) of the hemoglobin gene from both parents. In such individuals, the hemoglobin in red blood cells is extremely sensitive to oxygen deprivation, which results in shorter life expectancy. A person who inherits the sickle cell gene from one parent and a normal hemoglobin allele (HgbA) from the other, has a normal life expectancy. However, these heterozygote individuals, known as ""carriers"" of the sickle cell trait, may suffer problems from time to time. The heterozygote"
"50% chance of inheriting their mother's mutation, of being a haemophiliac (sons) or carrier (daughters). The daughter of a male haemophiliac will always inherit his mutation, while a son cannot ever inherit it. A female will only be affected with haemophilia in the rare circumstance that she inherits mutated X chromosomes from both a haemophiliac father and a carrier mother. No case of such double inheritance is known among Queen Victoria's descendants. Although an individual's haemophilia can usually be traced in the ancestry, in about 30% of cases there is no family history of the disorder, and the condition is"
"the gene for it. The last descendant of Victoria known to suffer from the disease was Infante Don Gonzalo, born in 1914, although dozens of descendants of Queen Victoria's (including males descended only through females) have been born since 1914. However, because the haemophilia gene usually remains hidden in females who only inherit the gene from one parent, and female descendants of Victoria have left many descendants in royal and noble families, there remains a small chance that the disease could appear again, especially among the female-line Spanish descendants of Princess Beatrice. Queen Victoria died in 1901 so she lived"
"to be homozygous to show a recessive trait. The heterogametic sex (males in humans) only receives one of each sex chromosome and will therefore show recessive trait even if they have only inherited one copy of a recessive allele. Haemophilia and red-green colour blindness are recessive, X-linked, pseudodominant genetic disorders, expressed mainly in human males because human females need to be homozygous (i.e., to have inherited the recessive allele from both parents) to show these traits. Pseudodominance is also observed in some autosomal recessive conditions. This could happen in the cases of loss of the dominant allele (deletion) or of"
"may be carriers of the condition. As with all genetic disorders, it is of course also possible for a human to acquire it spontaneously through mutation, rather than inheriting it, because of a new mutation in one of their parents' gametes. Spontaneous mutations account for about 33% of all cases of haemophilia A. About 30% of cases of haemophilia B are the result of a spontaneous gene mutation. If a female gives birth to a haemophiliac son, either the female is a carrier for the blood disorder or the haemophilia was the result of a spontaneous mutation. Until modern direct"
"a parasitic lifestyle in which it is entirely dependent upon host cells for the amino acids, fatty acids, and vitamins it has lost the ability to synthesize. Consistent with its parasitic lifestyle, the ""M. haemofelis"" genome contains a significant number of genes devoted to adhesins, resistance to oxidative stress, and the production of variable surface antigens that allow it to persist in the host. Once in the blood stream, ""M. haemofelis"" individuals adhere to the cell membranes of red blood cells and eventually become partially embedded. After a delay of 2 to 34 days, the acute phase of infection occurs"
"of gene therapy are in early human trials. Haemophilia A affects about 1 in 5,000–10,000, while haemophilia B affects about 1 in 40,000, males at birth. As haemophilia A and B are both X-linked recessive disorders, females are rarely severely affected. Some females with a nonfunctional gene on one of the X chromosomes may be mildly symptomatic. Haemophilia C occurs equally in both sexes and is mostly found in Ashkenazi Jews. In the 1800s haemophilia was common within the royal families of Europe. The difference between haemophilia A and B was determined in 1952. The word is from the Greek"
"reportedly has a median overall survival time of 4.8 months and 1, 3, and 5 year overall survival rates of 30%, 18%, and 17%, respectively. Human herpes virus-positive germinotropic lymphproliferative disorder (HHV+ GLPD) is an extremely rare disorder characterized by the localized swelling of lymph nodes due to the infiltration by plasmablasts (i.e. immature plasma cells). The disorder generally occurs in immune-competent individuals although it has been reported to occur in HIV-positive individuals. In most cases, the involved lymph nodes have a normal architecture with clusters of plasmablasts that are not only HHV8+ but also EBV+ with EBV likely being"
"is an autosomal recessive disorder, people who are heterozygotes for this still have an increased risk of developing a lymphoproliferative disorder. Viral infection is a very common cause of lymphoproliferative disorders. In children, the most common is believed to be congenital HIV infection because it is highly associated with acquired immunodeficiency, which often leads to lymphoproliferative disorders. There are many lymphoproliferative disorders that are associated with organ transplantation and immunosuppressant therapies. In most reported cases, these cause B cell lymphoproliferative disorders; however, some T cell variations have been described. The T cell variations are usually caused by the prolonged use"
"Chronic neutrophilic leukemia Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative neoplasm that features a persistent neutrophilia in peripheral blood, myeloid hyperplasia in bone marrow, hepatosplenomegaly, and the absence of the Philadelphia chromosome or a BCR/ABL fusion gene. The most common clinical finding is hepatosplenomegaly. Pruritus, gout, and mucocutaneous bleeding are occasionally seen. The cause of CNL is currently unknown. An association between CNL and multiple myeloma has been suggested based on the observation of myeloma in 20% of CNL cases. However, a clonal genetic abnormality has not been detected in these myeloma-associated cases of CNL, raising the possibility that"
"produce enough of its own. A study published in 1986 showed that 76% of those who used commercial Factor products became infected with HIV, as opposed to none of those who only used previous treatment, Cryoprecipitate. No government, healthcare or pharmaceutical entity in the UK has admitted any liability in the scandal, and no damages or compensation have been paid to those infected or affected, although the government has provided some means-tested benefits to some of the surviving victims through a Trust. Haemophilia is a mostly inherited genetic disorder that impairs the body's ability to clot, a process needed to"
"commonly progresses to include thrombocytopenia, increases susceptibility to infections due to, e.g. atypical mycobacteria or human papillomavirus, dysfunction of non-hematological organs, MDS, and leukemia (primarily AML and less commonly CMML). It is estimated that by age 30, 60% of these individuals develop leukemia. Some of these individuals have large deletion mutations that span the ""GATA2"" along with nearby genes and exhibit in addition to hematological defects various developmental abnormalities, neurological abnormalities, and/or body dysmorphic disorders. GATA2 deficiency has been diagnosed in up to 10% of individuals presenting with aplastic anemia. It is also the most common cause of hereditary bone"
"rare Haemophilia B. The sex-linked X chromosome disorder manifests almost exclusively in males, even though the genetic mutation causing the disorder is located on the X chromosome and can be inherited from the mother by male children or from either mother or father by female children. This is because the trait is recessive, meaning that only one correctly-functioning copy of the blood clotting factor gene is necessary for normal clotting. Females have two X chromosomes, and hence redundant copies of the blood clotting factor gene located on them. A female who inherits a mutated copy on one X chromosome has"
"7, with this macrocytosis being the first haematological marker. Defective in vitro haematopoiesis has been recorded for over two decades resulting from mutated FANCA proteins, in particular developmental defects such as impaired granulomonocytopoiesis due to FANCA mutation. Studies using clonogenic myeloid progenitors (CFU-GM) have also shown that the frequency of CFU-GM in normal bone marrow increased and their proliferative capacity decreased exponentially with age, with a particularly marked proliferative impairment in Fanconi anaemia afflicted children compared to age-matched healthy controls. As haematopoietic progenitor cell function begins at birth and continues throughout life, it is easily inferred that prolonged incapacitation of"