In pyruvate kinase (PK) deficiency red blood cells break apart more easily (hemolysis), causing hemolytic anemia. The defective gene present in a patient is replaced with a normal gene to enable the production of the active enzyme. Gallbladder removal (cholecystectomy) is pursued in individuals with symptomatic gallstones and in individuals at the time of splenectomy. The hemoglobin response is more likely in patients with certain PKLR genotypes. Jaundice is caused by high levels of bilirubin in the body. Gallstones are small, hard masses that form in the gallbladder and block the bile ducts and cause pain. Researchers are also studying a compound called mitapivat (AG-348) that acts to increase the activity of the pyruvate kinase enzyme in red blood cells. 2015;90:825-830. https://onlinelibrary.wiley.com/doi/full/10.1002/ajh.24088. Sickle cell disease causes chronic hemolysis and can be associated with episodes of pain and increased risk of infection and stroke, among other complications. Acquired hemolytic anemias Autoimmune hemolytic anemia is an acquired hemolytic anemia that develops when an individual’s immune system attacks their own red blood cells. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. Pediatricians or general internists, physicians who specialize in diagnosing and treating blood disorders (hematologists), and other healthcare professionals may need to systematically and comprehensively plan treatment. The degree of jaundice or scleral icterus is linked to the amount of total unconjugated bilirubin. Without pyruvate kinase, red blood … Red blood cells are formed in the bone marrow and then are released into the bloodstream. Newborns Before birth, some developing fetuses with anemia can develop a condition called fetal hydrops. Most individuals with PKD have different variants affecting each copy of the disease genes (compound heterozygotes). Because PK deficiency is rare, a registry for individuals with PK deficiency was developed to understand more about the variability and types of symptoms, complications, and treatments for this rare anemia. An aplastic crisis is caused by parvovirus B19 infection (also called Fifth disease). In the initial study, mitapivat raised the hemoglobin at least 1 g/dL in half of the adult participants in the trial. This can lead to anemia (not enough red blood cells). Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common red cell enzyme defect and is a genetic metabolic disorder caused by deficiency of the enzyme, G6PD. Red cell permeability defects: Hereditary xerocytosis and related disorders are hemolytic conditions caused by abnormal water content within the red cells. Treatment Treatment may require the coordinated efforts of a team of specialists. Vitamin D, calcium, and exercise may be important for bone health. An enlarged spleen does not typically cause pain. Gilbert syndrome is common, so it is possible for someone to inherit both PKD and Gilbert syndrome. Supportive care can include gallbladder monitoring due to risk of gallstones. Pyruvate kinase deficiency (PKDef) is an inherited hemolytic anemia caused by a defect in the enzyme pyruvate kinase. This has been pursued in a limited number of individuals, particularly individuals who require chronic blood transfusions. Pyruvate kinase deficiency is a rare disorder that affects both men and women. The PKLR gene contains instructions for creating (encoding) a specialized protein (enzyme) known as pyruvate kinase. People with this disorder have a condition known as chronic hemolytic anemia, in … It is the second most common RBC enzyme defect but is the … This type of bilirubin is called unconjugated (or indirect) bilirubin. The risk is the same for males and females. Pyruvate kinase deficiency is a genetic disorder that is autosomal recessive. PKD is caused by alterations (mutations) in the PKLR gene, which lead to a deficiency of the enzyme pyruvate kinase. PK Deficiency Whether you’ve recently been diagnosed, or you’ve been living with pyruvate kinase (PK) deficiency for years, learning as much as you can is important. Because this enzyme is deficient, there is a lack of ATP. Given the permanent transfer of the normal gene, it could theoretically lead to a “cure”. If we don't have a program for you now, please continue to check back with us. Genetic testing is useful: A blood transfusion may be necessary for the developing fetus (intrauterine transfusion) if there are signs of poor growth related to anemia during pregnancy. Signs of hemolysis include a low hemoglobin level, an elevated unconjugated bilirubin level, an elevated reticulocyte count, and low levels of haptoglobin in the blood. With hemolysis, an excess of bilirubin is released into the bloodstream and the liver cannot keep up with the conjugation process. PK deficiency; PKD. In infants, children, and adolescents with PK deficiency, blood transfusions may be used. Pyruvate Kinase Deficiency: Understanding and living with PKD https://pyruvatekinasedeficiency.com/. Most people with pyruvate kinase deficiency … Subsequently abnormalities of other glycolytic enzymes have also … Symptoms from pyruvate kinase deficiency can be highly variable. Anemia can cause tiredness, fatigue, increased need for sleep, weakness, lightheadedness, dizziness, irritability, headaches, pale skin color, difficulty breathing (dyspnea), shortness of breath, and cardiac symptoms. Without this enzyme, red blood cells break down too easily, resulting in a low level of these cells (hemolytic anemia). For the specific diagnosis of PK deficiency, further blood tests to measure pyruvate kinase enzyme activity may be necessary. Individuals may print one hard copy of an individual disease for personal use, provided that content is unmodified and includes NORD’s copyright. Aplastic crises in individuals with PKD often require a blood transfusion. G6PD deficiency is most commonly an episodic disorder triggered by certain medications or by eating fava beans. To search for patient organizations and other pages related to this topic, use the Advanced Search function at the top right corner of the page. In some newborns with severe jaundice, a special type of transfusion called an exchange transfusion may be necessary. Pyruvate kinase deficiency (PKD) is a rare genetic disorder characterized by the premature destruction of red bloods, which is called hemolytic anemia. If this is the case, PK enzyme activity may be compared to that of other red blood cell enzymes, which may be higher in comparison. Sometimes, the surgical removal of the spleen (splenectomy) may be recommended. 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. Blood. Removal the spleen may be considered if individuals require frequent blood transfusions or have frequent symptoms from anemia. Red cell pyruvate kinase deficiency is the most common cause of hereditary nonspherocytic hemolytic anemia. More research is necessary to determine the long-term safety and effectiveness of mitapivat for individuals with PK deficiency. The altered red blood cell has a shortened lifespan leading to hemolytic anemia. Molecular genetic testing can detect mutations in the PKLR gene known to cause the disorder. Phlebotomy (regular removal of blood) can be used to unload iron from the body but is often not well-tolerated in individuals with anemia. In gene therapy, the defective gene present in a patient is replaced with a normal gene to enable the production of the active enzyme. Pyruvate kinase (PK) deficiency is an inherited disease occasionally encountered in Abyssinian and Somali cats, and also reported rarely in the domestic shorthair cat. Vitamin D, calcium, and exercise may be important for bone health. Genes provide instructions for creating proteins that play a critical role in many functions of the body. Other individuals may have mild or no symptoms of the disorder and go undiagnosed into adulthood. However, at this time, this is under consideration as a research therapy only. Splenectomy, both open surgical and laparoscopic, has led to a partial improvement of the anemia in most, but not all, individuals. During these episodes, an individual’s symptoms worsen, such as fatigue, paleness, scleral icterus, jaundice and/or dark urine. Anemia is a general term for when there are low … An exchange transfusion is when an individual’s blood is removed and replaced by a donor’s blood. Loss of function of this enzyme results in premature death of red blood cells. Given the risk of infection after splenectomy, most individuals wait until at least the age of 5 years before proceeding with splenectomy. It is also important that individuals receive additional vaccines prior to splenectomy, take prophylactic antibiotics after splenectomy, and follow strict fever guidelines. The risk for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/. Red blood cells use several enzymes to ensure proper energy production. Available at: https://www.uptodate.com/contents/pyruvate-kinase-deficiency Accessed August 2019. This jaundice is usually more severe than physiologic jaundice that newborns typically develop between days 2 and 5 of life. Van Wijk R. Pyruvate kinase deficiency. Gallbladder removal (cholecystectomy) is pursued in individuals with symptomatic gallstones and in individuals at the time of splenectomy. Clinical Testing and Workup Initial lab tests may be performed to determine that anemia is present and whether it is due to hemolysis. https://www.ncbi.nlm.nih.gov/pubmed/30213831, Yacobovich J, Tamary H. Splenectomy and emerging novel treatments in rare inherited hemolytic anemias. active hemolysis), a detailed patient and family history, a thorough clinical evaluation, and a variety of specialized tests. First, your doctor will take a blood sample to send for laboratory testing to see if hemolytic anemia is present. Pyruvate kinase deficiency is an inherited disorder that affects red blood cells, which carry oxygen to the body's tissues. Disorders inherited in a recessive pattern occur when an individual inherits two variants in a gene for the same trait, one from each parent. Safe and efficient gene therapy for pyruvate kinase deficiency. This means that each parent carries the defective gene for this disease. Gene therapy is being studied as an approach to therapy for individuals with PK deficiency. Healthy red blood cells last approximately 120 days. Pyruvate kinase deficiency … Pyruvate kinase deficiency, one of the most common enzymatic defects of the erythrocyte, manifests clinically as a hemolytic anemia that can range from a mildly compensated … In allogeneic stem cell transplantation, affected individuals, after treatment with chemotherapy, receive hematopoietic stem cells from a healthy donor. Chelation agents bind with iron to form substances that can be excreted from the body easily. In clinical practice, the frequency is closer to 1 in 1,000,000 people. Pregnancy can also be a common hemolytic trigger. The medical term for jaundice is hyperbilirubinemia. Clinical spectrum of pyruvate kinase deficiency: data from the pyruvate kinase deficiency natural history study. Pyruvate kinase deficiency is caused by an alteration in the PKLR gene. National Organization for Rare Disorders (NORD) 55 Kenosia Ave., Danbury CT 06810 • (203)744-0100. Orphanet Encyclopedia, March 2009. Other individuals may never have a blood transfusion. Comparisons may be useful for a differential diagnosis. Affected individuals can also develop an enlarged spleen (splenomegaly). Pyruvate kinase deficiency is the second most common cause of enzyme-deficient hemolytic anemia, following G6PD deficiency. Adults can develop skin sores (ulcers), typically around the ankles. Blood. Initial studies have shown that this twice daily, oral compound may be both effective and well tolerated. Copyright ©2020 NORD - National Organization for Rare Disorders, Inc. All rights reserved. Most newborns with PK deficiency will develop jaundice because of the breakdown of red cells and the inability of their immature livers to conjugate bilirubin. This helps to speed up the bilirubin metabolism and excretion. Haematologica. Pyruvate kinase deficiency is a condition in which red blood cells break down faster than they should. Erythrocyte pyruvate kinase deficiency: 2015 status report. Sometimes, the surgical removal of the spleen, known as a splenectomy, may be recommended. The burden of disease in pyruvate kinase deficiency: patients’ perception of the impact of health-related quality of life. Pyruvate kinase deficiency is a condition in which red blood cells break down faster than they should. Others may only be transfused for acute infections. This is a major medical procedure that carries significant risk, including dying from complications related to transplant. Red cell transfusions cause a buildup of iron over time. HemaSphere. Iron overload occurs commonly in individuals with PK deficiency, even in the absence of red cell transfusions, through increased absorption from the diet. Pyruvate kinase deficiency (PKD) is one of the most common enzymatic defects of the RBCs, it manifests clinically as hemolytic anemia that can range from mild to severe. During this procedure, intense light is focused on the bare skin, while the eyes are shielded. Your doctor will take a blood sample to send to a specialized laboratory to ensure the accuracy of the test. Energy is produced through a chemical process called glycolysis. More research is necessary to determine the long-term safety and effectiveness of this therapy for individuals with PK deficiency. https://www.ncbi.nlm.nih.gov/pubmed/29242305, Kung C, Hixon J, Kosinski PA, et al. NORD is not a medical provider or health care facility and thus can neither diagnose any disease or disorder nor endorse or recommend any specific medical treatments. The chance for a child to receive working genes from both parents is 25%. NORD is a registered 501(c)(3) charity organization. Pyruvate kinase deficiency is an inherited disorder that affects red blood cells, which carry oxygen to the body’s tissues. Shear within the blood vessels can also cause hemolysis. It is also important that individuals receive additional vaccines prior to splenectomy, take prophylactic antibiotics after splenectomy, and follow strict fever guidelines. It is not uncommon for newborns with PK deficiency to develop jaundice(yellowing of the skin) in the first day of life. 2018 Feb;103(2):e82-e86. Chelation agents bind with iron to form substances that can be excreted from the body easily. Both autosomal dominant and recessive inheritance have been observed with the disorder; classically, and more commonly, the inheritance is autosomal recessive. This test is only run at specialized laboratories; most clinics and hospitals send this test to be run at these specialized centers. Also, the disease … UpToDate, Inc. 2018 Jun 18. Pyruvate kinase deficiency (PKD) is the most common cause of chronic hereditary non-spherocytic hemolytic anemia and results in a broad spectrum of disease. This is a serious condition in which large amounts of fluid builds up in the tissues and organs of the fetus. However, this surgical procedure carries potential risks such as life-threatening bloodstream infections and blood clot formation (thrombosis), which are weighed against the potential benefits of splenectomy in each individual. Pyruvate kinase deficiency. This helps to speed up the bilirubin metabolism and excretion. During this procedure, intense light is focused on the bare skin, while the eyes are shielded. Other less common complications include high blood pressure in the arteries in the lungs and the right side of the heart (pulmonary hypertension) and blood cell production outside of the bone marrow (extramedullary hematopoiesis). In individuals with PKD, parvovirus infection reduces or stops reticulocyte production in the bone marrow and thereby decreases the hemoglobin level. Pyruvate kinase is an enzyme … Without this enzyme, red blood cells break down too easily, resulting in a low … Infections and medications can cause direct destruction of red cells. Children and Adults The most common finding in children and adults is anemia. However, this surgical procedure carries potential risks such as life-threatening bloodstream infections and blood clot formation (thrombosis), which are weighed against the potential benefits of splenectomy in each individual. As the altered red cells are destroyed, new red cells (reticulocytes) are created, creating a balance of increased red cell destruction and increased red cell production. Hemolytic episodes develop in the presence of stressors or triggers of hemolysis, which most often are infections and, therefore, more frequent in childhood. In allogeneic stem cell transplantation, affected individuals, after treatment with chemotherapy, receive hematopoietic stem cells from a healthy donor. In the initial study, mitapivat raised the hemoglobin at least 1 g/dL in about 50% of the adult participants in the trial. Given the permanent transfer of the normal gene, it could theoretically lead to a “cure.” However, at this time, this is under consideration as a research therapy only. Removal of the spleen may be considered if individuals require frequent blood transfusions or have frequent symptoms from anemia. The body does not have a mechanism for getting rid of iron and so with repeated red cell transfusions, iron begins to deposit in the liver. Iron overload is the abnormal accumulation of iron in various organs of the body most commonly in the liver, but iron loading can also occur in the heart and hormone-producing organs (endocrine organs). Some of these disorders are associated with infections. Although the gene is not expressed in … Symptoms of the following disorders can be similar to those of pyruvate kinase deficiency. Mol Ther. Iron overload occurs commonly in individuals with PKD, even in the absence of red cell transfusions, through increased absorption from the diet. Internationally, PKD has been reported in … Red cell transfusions cause a buildup of iron over time. Others may only be transfused for acute infections or in pregnancy. Red cells rely on this process for energy, and so, pyruvate kinase deficiency leads to a deficiency in energy and to premature red cell destruction (hemolysis). Symptoms of PK deficiency can begin early in life. Unlike children and adults with elevated bilirubin levels, high bilirubin levels in infants can lead to kernicterus, a neurologic condition characterized by the accumulation of toxic levels of bilirubin. Given the risk of infection after splenectomy, most individuals wait until at least the age of 5 years before proceeding with splenectomy. Your doctor will take a blood sample to send to a specialized laboratory to ensure the accuracy of the test. Br J Haematol. NORD strives to open new assistance programs as funding allows. At birth, some infants may have significant anemia and severe jaundice, which is yellowing of … Pyruvate kinase deficiency. The content of the website and databases of the National Organization for Rare Disorders (NORD) is copyrighted and may not be reproduced, copied, downloaded or disseminated, in any way, for any commercial or public purpose, without prior written authorization and approval from NORD. Pyruvate kinase deficiency (PKD) affects both genders equally and occurs in all races (a high incidence has been reported in Amish people from Pennsylvania). The diagnosis of PKD requires a high index of suspicion and judicious use of laboratory tests that may not always be informative, including pyruvate kinase … The body does not have a mechanism for getting rid of iron and so with repeated red cell transfusions, iron begins to deposit in the liver. Pyruvate kinase is an enzyme that helps cells turn sugar (glucose) into energy (called adenosine triphosphate, ATP) in a process called glycolysis. … The goal is to avoid transfusions if possible, but they may be necessary, particularly in the first years of life, to support growth and development and avoid symptoms, such as fatigue or poor feeding. In older children, there are no standard criteria or schedule for transfusions, especially since the symptoms differ so widely between individuals. April 2012. People with pyruvate kinase deficiency have a condition known as chronic hemolytic … Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal disorder of hematopoietic stem cells characterized by chronic hemolysis, thrombosis (blot clots), increased risk of infections, and bone marrow failure. Am J Hemtaol. Instead of lasting 120 days, red cells with pyruvate kinase deficiency last only a few days to weeks. The hemoglobin response is more likely in patients with certain PKLR genotypes. We all have Pyruvate Kinase Deficiency and feel the need to have access to comprehensible information about this rare disorder. One function of the spleen is to filter red blood cells. Safety and efficacy of mitapivat in pyruvate kinase deficiency. This is a major medical procedure that carries significant risk. This can lead to anemia (not enough red blood cells). Other complications can occur in PKD. Pyruvate kinase deficiency (PKD) is a rare genetic disorder characterized by the premature destruction of red bloods, which is called hemolytic anemia. Hemolytic anemia due to deficiency of erythrocytic pyruvate kinase is a rare autosomal recessive disorder. The frequency of the disorder is unknown, although one estimate suggests that approximately 1 in 20,000 Caucasian people develop the disorder. 2018;131:2183-2192. https://www.ncbi.nlm.nih.gov/pubmed/29549173, Grace RF, Cohen J, Egan S, et al. Patients with a pyruvate kinase deficiency typically experience serious complications, such as gallstones, pulmonary hypertension osteoporosis and iron overload. For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database. In older children and adults, there are no standard criteria or schedule for transfusions, especially since the symptoms differ so widely between individuals. These abnormal shapes cause the red cells to more easily break apart in the spleen. Pyruvate kinase (PK) deficiency is an autosomal recessive disorder with clinical manifestations of non-spherocytic hemolytic anemia in homozygotes or double heterozygotes. Most people with PK deficiency have 5–25% of the normal enzyme activity. For individuals with daily symptoms from anemia, regular blood transfusions may be recommended. Pyruvate Kinase Deficiency. Folic acid supplementation, which supports increased red cell production, is often prescribed. Pyruvate kinase deficiency is an inherited metabolic disorder of the enzyme pyruvate kinase which affects the survival of red blood cells. Pyruvate kinase deficiency is an inherited lack of the enzyme pyruvate kinase, which is used by red blood cells. Most people with pyruvate kinase deficiency … Pyruvate kinase deficiency is an inherited lack of the enzyme pyruvate kinase, which is used by red blood cells. An exchange transfusion is when an individual’s blood is removed and replaced by a donor’s blood. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but, with the carrier state for PKD, will not show symptoms. In some instances, the disorder can be life-threatening at birth. Newborns A blood transfusion may be necessary for the developing fetus (intrauterine transfusion) if fetal hydrops develops or there are signs of poor growth related to anemia during pregnancy . PK deficiency is present from birth. https://journals.lww.com/hemasphere/Fulltext/2019/06002/Splenectomy_and_emerging_novel_treatments_in_rare.60.aspx, Grace RF, Bianchi P, van Beers EJ, et al. Pyruvate kinase (PK) deficiency is an inherited (autosomal recessive) red blood cell (RBC) enzyme disorder that causes chronic hemolysis. Infants, Children, and Adults In infants, children, and adults with PKD, blood transfusions may be used. 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