Glycogenosis type XI (Lactate dehydrogenase deficiency, Glycogen storage disease type XI) - LDHA and LDHB genes.
Lactate dehydrogenase deficiency is a condition that affects the way the body breaks down glucose for energy in cells, especially in muscle cells. Two types of lactate dehydrogenase deficiency have been described: lactate dehydrogenase deficiency type A (sometimes called glycogenosis type XI) and lactate dehydrogenase deficiency type B.
People with lactate dehydrogenase deficiency type A manifest fatigue, muscle pain and cramps during exercise. In some people with type A, high-intensity exercise or other strenuous activity leads to rhabdomyolysis. The destruction of muscle tissue releases myoglobin, which is processed by the kidneys and released into the urine. Myoglobin makes the urine red or brown. This protein can also damage the kidneys and, in some cases, leads to a potentially fatal renal failure. Some people with type A develop skin rashes. The severity of signs and symptoms among people with lactate dehydrogenase A deficiency is very variable.
Meanwhile, people with type B disease usually have no signs or symptoms associated. They have no difficulty with physical activity or any of the specific physical functions related to alteration. In these individuals, the disease is detected only when a blood analysis reveals a reduction in lactate dehydrogenase activity.
This process is due to mutations in LDHA gene located on the short arm of chromosome 11 (11p15.4) and LDHB gene located on the short arm of chromosome 12 (12p12.2-p12.1). These genes, encoding subunits lactate dehydrogenase-A and lactate dehydrogenase-B of the lactate dehydrogenase enzyme. This enzyme is found throughout the body and is important for the production of energy for cells. There are five different forms of this enzyme, each consisting of four protein subunits. Various combinations of subunits lactate dehydrogenase-A and lactate dehydrogenase-B represent different forms of the enzyme. Version of lactate dehydrogenase comprised by four subunits of lactate dehydrogenase-A is found mainly in skeletal muscles. Skeletal muscles require large amounts of energy during high intensity exercise when the oxygen consumption of the organism is not sufficient for the amount of energy required. During anaerobic exercise, lactate dehydrogenase enzyme is involved in the breakdown of glucose stored in muscles (as glycogen) to create additional energy. During the final stage of the degradation of glycogen, lactate dehydrogenase converts a molecule called pyruvate to a similar molecule called lactate. Version of lactate dehydrogenase comprised by four subunits of lactate dehydrogenase-B is found mainly in the heart muscle. This version of the enzyme converts lactate to pyruvate.
They have identified at least eight mutations in the LDHA gene leading to deficiency of lactate dehydrogenase type A. These mutations result encoding a subunit of lactate dehydrogenase-A that cannot bind to other subunits to form lactate dehydrogenase. Consequently, glycogen is not decomposed efficiently, leading to a decreased energy in muscle cells. When muscle cells do not get enough energy during strenuous physical activity, muscles weaken and muscle tissue may decompose. Meanwhile, more than 15 mutations in the LDHB gene have been described leading to lactate dehydrogenase deficiency type B. Most of these gene mutations change the amino acids in lactate dehydrogenase-B subunit. These mutations lead to a lactic dehydrogenase-B subunit that cannot bind to other subunits to form lactate dehydrogenase. Although the lactate dehydrogenase activity is reduced in heart muscle cells of people with deficiency of lactate dehydrogenase type B, which does not seem to have any signs or symptoms related to the disease it is not clear why this type of deficiency the enzyme does not cause any health problems.
This disease is inherited in an autosomal recessive pattern, that is, 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 lactate dehydrogenase deficiency, by complete PCR amplification of the exons of LDHA and LDHB genes, respectively, 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).