Red cell pyruvate kinase deficiency is a hereditary blood disorder characterized by a deficiency of the enzyme pyruvate kinase. Physical findings associated with the disorder may include reduced levels of oxygen-carrying hemoglobulin in the blood due to premature destruction of red blood cells (hemolytic anemia); abnormally increased levels of bilirubin in the blood (hyperbilirubinemia); abnormal enlargement of the spleen (splenomegaly); and/or other abnormalities. Pyruvate kinase deficiency is inherited as an autosomal recessive genetic trait. It is one of a group of diseases known as hereditary nonspherocytic hemolytic anemias. (Nonspherocytic refers to the fact that the red blood cells do not assume a spherical shape, as they do with some blood disorders.
Pyruvate kinase deficiency is characterized by hemolytic anemia. An excess of young red blood cells (reticulocytes) usually occurs. The anemia is chronic and may vary from mild to severe. Enlargement of the spleen (splenomegaly) may occur, and gallstones may sometimes develop. After infections, the anemia tends to become more severe. In rare cases, leg ulcers may develop.
Pyruvate kinase deficiency is inherited in an autosomal-recessive manner. It is caused by mutations of the PKLR gene, the gene that encodes the liver and red cell type of pyruvate kinase. The gene is located on chromosome 1 (1q21).
Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22, and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated p and a long arm designated q. Chromosomes are further sub-divided into many bands that are numbered. For example, chromosome 1q21 refers to band 21 on the long arm of chromosome 1. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.
Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.
All individuals carry a few abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
The incidence of pyruvate kinase deficiency is less than 1% of the population. Males and females are affected in equal numbers. Most affected persons identified thus far have been of European origin.
A physical examination that reveals an enlarged spleen in the presence of jaundice is usually sufficient to trigger a call for more definitive tests. A complete blood count, differential blood counts, and reticulocyte counts may be undertaken. Tests for the presence of bile salts (bilirubin) are used to determine whether the gall bladder is involved. DNA analysis may be ordered to confirm the diagnosis.
Mild cases require no treatment. More severe disease is usually treated with blood transfusions. Surgical removal of the spleen (splenectomy) may also be needed. With small children, this is delayed as long as possible to allow the immune system to mature. Other treatment is symptomatic and supportive.
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