Methylenetetrahydrofolate reductase deficiency is the most common genetic cause of elevated serum levels of homocysteine (hyperhomocysteinemia). It is caused by genetic defects in MTHFR, which is an important enzyme in the methyl cycle.Common variants of MTHFR deficiency are asymptomatic and have only minor effects on disease risk. Severe variants (from nonsense mutations) are vanishingly rare. Symptoms
The common MTHFR deficiencies are usually asymptomatic, although the 677T variant can cause a mildly increased risk of some diseases. For individuals homozygous in the 677T variant, there is a mildly elevated risk of thromboembolism (odds ratio 1.2), and stroke (odds ratio 1.26). There is also an elevated risk of neural tube defects among children of individuals with the C677T polymorphism (odds ratio 1.38).For cardiovascular risk, common MTHFR deficiencies were once thought to be associated but meta-analyses indicate that correlation this was an artifact of publication bias. Causes
MTHFR is the rate-limiting enzyme in the methyl cycle, which includes the conversion of homocysteine into methionine. Defects in variants of MTHFR can therefore lead to hyperhomocysteinemia.There are two common variants of MTHFR deficiency. In the more significant of the two, the individual is homozygous for the 677T polymorphism. This variant in particular is the most common genetic cause of hyperhomocysteinemia. The resulting enzyme is thermolabile and in homozygotes, enzymatic activity is depressed to 35% of its usual level. The second variant is a milder one, caused by a homologous 1298C polymorphism. This leads to 68% of the control values of enzyme activity, and it normally does not lead to low serum folate.
Epidemiology
Most arboviruses are located in tropical areas, however as a group they have a global distribution. The warm climate conditions found in tropical areas allows for year-round transmission by the arthropod vectors. Other important factors determining geographic distribution of arthropod vectors include rainfall, humidity, and vegetation.Mapping methods such as GIS and GPS have allowed for spatial and temporal analyses of arboviruses. Tagging cases or breeding sites geographically has allowed for deeper examination of vector transmission.To see the epidemiology of specific arboviruses, the following resources hold maps, fact sheets, and reports on arboviruses and arboviral epidemics. History
Arboviruses were not known to exist until the rise of modern medicine, with the germ theory and an understanding that viruses were distinct from other microorganisms. The connection between arthropods and disease was not postulated until 1881 when Cuban doctor and scientist Carlos Finlay proposed that yellow fever may be transmitted by mosquitoes instead of human contact, a reality that was verified by Major Walter Reed in 1901. The primary vector, Aedes aegypti, had spread globally from the 15th to the 19th centuries as a result of globalization and the slave trade. This geographic spreading caused dengue fever epidemics throughout the 18th and 19th centuries, and later, in 1906, transmission by the Aedes mosquitoes was confirmed, making yellow fever and dengue fever the first two diseases known to be caused by viruses.Thomas Milton Rivers published the first clear description of a virus as distinct from a bacterium in 1927.