Prekallikrein deficiency (prekallikrein deficiency) - Gen KLKB1.
Prekallikrein deficiency is a blood disorder that usually does not lead to health problems. In affected individuals, the blood tests show a partial activated thromboplastin time (PTT), a result that is usually associated with bleeding problems. However, bleeding problems are not associated with prekallikrein deficiency. Some affected people have health problems related to blood clotting, such as a heart attack, stroke, deep vein thrombosis, nosebleeds, or excessive bleeding after surgery. However, these problems are common in the general population, and most affected individuals have other risk factors for its development, so it is unclear if their appearance is related to this disease.
This process is due to mutations in the gene KLKB1, located on the long arm of chromosome 4 (4q35). This gene encodes a protein called prekallikrein. Prekallikrein is synthesized in the liver and circulates in the blood. A molecule called factor XII converts prekallikrein in plasma kallikrein which helps to further activate the factor XII. Plasma kallikrein and factor XII are involved in the early stages of blood coagulation as part of a process called the intrinsic coagulation pathway, also called the contact activation pathway. Blood clotting protects the organism after injury to prevent bleeding. The interaction between plasma kallikrein and factor XII also initiates a series of chemical reactions leading to the release of bradykinin. Bradykinin promotes inflammation by increasing the permeability of the walls of blood vessels, allowing more fluids to leak into the body tissues. This leakage of fluids causes the swelling that accompanies inflammation.
They have identified at least 9 KLKB1 genetic mutations in people with prekallikrein deficiency. These genetic mutations reduce or eliminate the functional plasma kallikrein in the blood of affected individuals and probably impairs the intrinsic coagulation pathway. It is believed that this deficiency plasma kallikrein functional protein usually causes no symptoms because the extrinsic coagulation pathway, also known as tissue factor pathway can compensate the intrinsic pathway of coagulation impaired.
This disease is inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with prekallikrein deficiency, by complete PCR amplification of exons KLKB1 gene, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).