The prevalence of this deficiency is unknown, though some estimates have been made based on the frequency of low red cell pk activity in the population. Intravascular hemolysis results in hemoglobinemia when the amount of hemoglobin released into plasma exceeds the hemoglobinbinding capacity of the plasmabinding protein haptoglobin, a protein normally present in concentrations of about 100 mgdl 1. There is no treatment for pyruvate kinase deficiency, and affected dogs will have a shortened lifespan due to myelofibrosis and osteosclerosis of the bone marrow. Disorders of red blood cell enzymes, membranes, and hemoglobin cause hereditary hemolytic anemias. Patients affected with this chronic hemolytic anemia exhibit pale skin, jaundice, fatigue, dyspnea, and tachycardia. Surprisingly, however, the symptomatology is less severe than hematologic indices indicate. Autoimmune hemolytic anemia cancer therapy advisor. Additionally, decreased levels of plasma haptoglobin, a marker of rbc destruction, are evidenced1, 2, 3 regardless the site of hemolysis intravascular or extravascular. Other select causes of acquired hemolysis not discussed in this article include splenomegaly, endstage liver diseasespur cell acanthocyte hemolytic anemia, paroxysmal cold hemoglobinuria, paroxysmal nocturnal hemoglobinuria, insect stings, and spider bites.
Hemolysis can occur due to different causes and leads to the release of hemoglobin into the bloodstream. Pyruvate kinase deficiency is an inherited metabolic disorder of the enzyme pyruvate kinase which affects the survival of red blood cells. Without this crucial enzyme, the red blood cell breaks down more rapidly. Membranecytoskeletal defectshs, elliptocytosis, ovalocytosis,stomatocytosis aquired red cell membrane abnormalitypnh. Philip lanzkowsky, in lanzkowskys manual of pediatric hematology and.
Pyruvate kinase pk deficiency is a rare cause of neonatal hemolytic jaundice, with. Autosomal recessive mutation in the beta chain of hemoglobin. Safety and efficacy of mitapivat in pyruvate kinase deficiency. Pyruvate kinase deficiency and hemolytic anemia quizlet. Pyruvate kinase deficiency is an inherited lack of the enzyme pyruvate kinase, which is used by red blood cells. Pyruvate kinase deficiency and related disorders of red cell.
Pyruvate kinase deficiency hemolytic anemia youtube. Pyruvate kinase deficiency pkd is a rare genetic disorder characterized by the premature destruction of red bloods, which is called hemolytic anemia. Erythrocytic pyruvate kinase mutations causing hemolytic anemia, osteosclerosis, and secondary hemochromatosis in dogs g. For language access assistance, contact the ncats public information officer. Pyruvate kinase converts phosphoenolpyruvate to pyruvate, creating 50% of the red cell total atp. Pyruvate kinase is an enzyme, or chemical, found within your red blood cells required to make energy. Properties of abnormal enzyme associated with hemolytic anemia in the basenji dog. Intravascular hemolysis and the pathophysiology of sickle cell disease article pdf available in journal of clinical investigation 1273. Pyruvate kinase deficiency or pkd is a hereditary disease caused by a lack of pyruvate kinase, an enzyme that plays an important role in the energy supply of the red blood cells. Hemolytic anemia is associated with complications that need monitoring, including the development of gallstones, iron overload and low bone density. Overview of hemolytic anemia hematology and oncology msd.
The pyruvate kinase test checks whether you have a pyruvate kinase deficiency, a genetic disorder that reduces the amount of red blood cells in your blood. 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 anemia to severe anemia of childhood. Pyruvate kinase deficiency is a rare genetic disorder characterized by. People with this disorder have a condition known as chronic hemolytic anemia, in which red blood cells are broken down undergo hemolysis prematurely, resulting in a shortage of red blood cells anemia.
Pdf over the last several decades, our understanding of the genetic variation, pathophysiology, and complications of the hemolytic anemia. The signs and symptoms of the disease may vary greatly from person to person. It catalyzes the transfer of a phosphate group from phosphoenolpyruvate pep to adenosine diphosphate adp, yielding one molecule of pyruvate and one molecule of atp. Anemia is a general term for when there are low levels of red blood cells in the bloodstream, and hemolytic or hemolysis means that the red blood cells break down prematurely. Neonatal hemolytic jaundice is a risk factor for kernicterus. Pyruvate kinase deficiency causes, symptoms, diagnosis. Molecular study of pyruvate kinase deficient patients with. One patient died, but the other two survived after an exchange transfusion.
Diagnosis of pyruvate kinase deficiency pyruvate kinase. Enzym defects g6pd deficiency, pyruvate kinase deficiency. Pulmonary arterial hypertension is an increasingly recognized complication of chronic hereditary and acquired hemolytic anemias, including scd, 22,51,6569 thalassemia intermedia and major, 7076 pnh, 77,78 hereditary spherocytosis and stomatocytosis, 7984 microangiopathic hemolytic anemias, 8591 and pyruvate kinase deficiency. Pyruvate kinase deficiency pkd is a relatively common enzymatic defect in red blood cells affecting an estimated one in 20,000 people and is the leading cause of hereditary nonspherocytic hemolytic anemia beutler and gelbart 2000. Pyruvate kinase deficiency omim 266200 is one of the most common causes of hereditary nonspherocytic hemolytic anemia and is associated with lifelong chronic hemolysis. Jan 01, 2007 the intravascular hemolysis is explained by a deficiency of glycosil phosphatidylinositol gpianchored complement regulatory proteins such as cd59 and cd55 on the membrane of red blood cells rbcs, but the mechanism responsible for the increased incidence of thrombotic events in pnh remains unclear. Red blood cells from heterozygous individuals possess only 40%60% of the pyruvate.
Defects in pyruvate kinase pk and phosphofructokinase pfk, key regulatory enzymes in anaerobic glycolysis, result in impaired atp production and shortened erythrocyte survival. When this technique was applied to the dna of 10 unrelated patients with pyruvate kinase deficiency, the following. Start studying pyruvate kinase deficiency and hemolytic anemia. Pyruvate kinase deficiency is a chronic hemolytic anemia caused by mutations in pkr, a key glycolytic enzyme in erythrocytes. Pyruvate kinase pk deficiency is the most common cause of congenital nonspherocytic chronic hemolytic anemia and is the result of an erythrocyte enzyme. Infectious agents such as malaria and babesiosis invade red blood cells. People with pyruvate kinase deficiency have a condition known as chronic hemolytic anemia, in which red blood cells are broken down undergo hemolysis prematurely, resulting in a shortage of red blood cells anemia. Hemolytic anemia due to deficiency of erythrocytic pyruvate kinase is a rare autosomal recessive disorder. Since pyruvate kinase deficiency is caused by a lack of the pyruvate kinase enzyme, a lower activity rate can confirm the diagnosis. Hemolytic anemia is associated with complications that. Hemolytic anemias are a group of conditions characterized by the breakdown of red blood cells. Atp deficiency intravascular hemolysis results in hemoglobinemia when the amount of hemoglobin released into plasma exceeds the hemoglobinbinding capacity of the plasmabinding protein haptoglobin, a protein normally present in concentrations of about 100 mgdl 1. Hemolytic anemia and pyruvate kinase deficiency in pregnancy. Red cell longevity is dependent on the atp produced in glycolysis fig.
Lr gene mutations and a retrospective survey of pk mutations in a small and selected group of beagles and west highland white terriers whwt. A presumption of pyruvate kinase deficiency can then be confirmed through a blood test measuring the enzyme activity rate of the pyruvate kinase enzyme. Check the full list of possible causes and conditions now. Phosphofructokinase deficiency can cause an intravascular hemolysis after exercise, due to rbc fragility in an alkaline ph a respiratory alkalosis is induced by exercise giger and harvey 1987. Learn vocabulary, terms, and more with flashcards, games, and other study tools. Without pyruvate kinase, red blood cells break down too easily, resulting in low levels of these cells hemolytic anemia. Red blood cell pk deficiency is the most frequent enzyme disorder leading to chronic nonspherocytic haemolytic anaemia. The deficiency of g6pd leads to hemolytic anemia in the face of oxidative stress see. Pyruvate kinase deficiency an overview sciencedirect. Hemolysis is caused by either abnormalities of the rbcs themselves abnormalities in hemoglobin, the rbc membrane or intracellular enzymes, also called corpuscular anemia, or by external causes immunemediated or mechanical damage, which is referred to as.
Pyruvate kinase pk deficiency is the most common cause of congenital nonspherocytic chronic hemolytic anemia and is the result of an. The clinical sequelae of intravascular hemolysis and. Hemolysis is caused by either abnormalities of the rbcs themselves abnormalities in hemoglobin, the rbc membrane or intracellular enzymes, also called corpuscular anemia, or by external causes immunemediated or mechanical damage, which is referred to as extracorpuscular anemia. Hemolysis, myopathy, and cardiac disease associated with.
The disorder is characterized by lifelong chronic hemolysis of variable severity. Diagnostic approach to hemolytic anemias in the adult. Pyruvate kinase deficiency pkd symptoms and treatment. Pyruvate kinase deficiency genetic and rare diseases. Patients display a highly variable degree of severity. Inheritance is mainly via autosomal recessive pattern, but autosomal dominant patterns have also been seen. Hemolysis is a fundamental feature of sickle cell anemia that contributes to its pathophysiology and phenotypic variability. This red blood cell breakdown is called hemolysis and pk deficiency is classified as a hemolytic anemia. Pregnancy complicated by pyruvate kinase deficiency is rare. Dic, shock, renal failure, death chronic hemolysis. Erythrocyte pyruvate kinase deficiency is inherited as an autosomal recessive disorder and mutations in the erythrocyte pyruvate kinase gene occur with a frequency of 1 in 10,000.
Animals labrador retrievers 2 siblings, 5 unrelated, pugs. Erythrocyte pyruvate kinase deficiency in nonspherocytic hemolytic anemia. It is the second most common cause of enzymedeficient hemolytic anemia. Pyruvate kinase deficient hemolytic anemia in the northern. Jul 01, 2012 background erythrocytic pyruvate kinase pk deficiency, first documented in basenjis, is the most common inherited erythroenzymopathy in dogs. Phenotypically it exhibits a variable range of anemia, from mild to transfusiondependent.
Jci intravascular hemolysis and the pathophysiology of. Coagulation in the pathophysiology of hemolytic anemias. G6pd deficiency, pyruvate kinase deficiency, and others. Deficiencies of most of the enzymes of the embdenmeyerhof glycolytic pathway, including pyruvate kinase pk, have been reported. Pyruvate kinase deficiencies are seen in basenjis, beagles, west highland white terriers, cairn terriers, and other breeds, as well as abyssinian and somali cats. If you have problems viewing pdf files, download the latest version of adobe reader. Pyruvate kinase pk deficiency is the most common cause of congenital non spherocytic chronic hemolytic anemia and is the result of an. These 2 phase 1 randomized, placebocontrolled, double. Both autosomal dominant and recessive inheritance have been observed with the disorder. Pyruvate kinase deficiency anemia symptoms, treatments. Pyruvate kinase deficiency is the second most common cause of enzymedeficient hemolytic anemia. Pdf pyruvate kinase deficiency and malaria gundula min. Erythrocytic pyruvate kinase mutations causing hemolytic.
Erythrocyte pyruvate kinase deficiency in nonspherocytic. Hemolytic anemia due to pyruvate kinase deficiency. Estimating the prevalence of pyruvate kinase deficiency. Pyruvate kinase pk deficiency is an inherited autosomal. Defective red cell metabolism as in glucose6phosphate dehydrogenase deficiency and pyruvate kinase deficiency. Pyruvate kinase pk is a key regulating enzyme of the glycolytic pathway involved in the production of atp metabolic energy. Pyruvate kinase deficiency hematology medbullets step 1. At that time, separate alleles or even genes at different loci were thought to be the possible bases for clinical variability. Normal red blood cells erythrocytes have a lifespan of about 120 days. Oligonucleotide primers for these determined intron sequences were used to sequence the exons. Pdf intravascular hemolysis and the pathophysiology of.
Three neonates with glucose6phosphate dehydrogenase g6pd deficiency are described. Pk deficiency, although relatively rare, is the erythrocyte enzyme deficiency most frequently found to be a cause of chronic nonspherocytic hemolytic anemia cnsha. When theres a shortage of the enzyme, the red blood cells wont be able. Jun 01, 2004 microangiopathic hemolytic anemia occurs when the red cell membrane is damaged in circulation, leading to intravascular hemolysis and the appearance of schistocytes. Red cell pyruvate kinase pk deficiency is the most frequent enzyme. Common symptoms reported by people with pyruvate kinase deficiency anemia. Pyruvate kinase deficiency is an autosomal recessive disorder that is less. Hemolytic anemia knowledge for medical students and. Oct 09, 2015 additionally, decreased levels of plasma haptoglobin, a marker of rbc destruction, are evidenced1, 2, 3 regardless the site of hemolysis intravascular or extravascular. Without this enzyme, red blood cells break down too easily, resulting in a low level of these cells hemolytic anemia. Averys diseases of the newborn ninth edition, 2012.
Pyruvate kinase was inappropriately named inconsistently with a conventional kinase before it was recognized that it did not directly. Red cell pyruvate kinase deficiency pkd is the most common glycolytic defect causing congenital non. Pyruvate kinase pk deficiency is a rare inherited form of anemia. Genetic and rare diseases information center gard po box 8126, gaithersburg, md 208988126. Electrophoretic, immunologic and kinetic characterization of erythrocyte pyruvate kinase in the basenji dog with pyruvate kinase deficiency. Glucose6phosphate dehydrogenase deficiency leads to. For marked intravascular hemolysis, maintenance of renal perfusion and urine output is. Concerned about the timing of jaundice and lack of any morphologic abnormalities, the pediatrician orders a functional assay to investigate pyruvate kinase. G6pd, pyruvate kinase deficiency hemoglobin synthesis disorders e. Pyruvate kinase pk deficiency is the most common cause of hereditary nonspherocytic hemolytic anemia. Pyruvate kinase, erythrocytes northwell health laboratories. All three patients suffered an episode of massive acute haemolysis, in the absence of blood group incompatibilities, infection, or ingestion of oxidising agents known to trigger haemolysis. Analysis of pyruvate kinasedeficiency mutations that. Decompartmentalized hemoglobin, arginase 1, asymmetric dimethylarginine, and adenine nucleotides are all products of hemolysis that promote vasomotor dysfunction, proliferative vasculopathy, and a multitude of clinical complications of pulmonary and systemic vasculopathy.
Dna analysis was performed on 30 unrelated patients with hereditary nonspherocytic hemolytic anemia hnsha who had been found to be pyruvate kinase pk deficient by enzyme assay. The intron sequences of the human ltype pyruvate kinase gene pklr were determined by using primers selected from the known cdna sequence. Pyruvate kinase deficiency an overview sciencedirect topics. Pyruvate kinase deficiency is a genetic blood disorder characterized by low levels of an enzyme called pyruvate kinase, which is used by red blood cells. Pyruvate kinase deficiency with hemolytic anemia via the. Pyruvate kinase deficiency is an autosomal recessive disorder that is less prevalent than g6pd deficiency and typically presents with jaundice, anemia, and reticulocytosis mentzer, 1993. Pyruvate kinase deficiency nord national organization. Pyruvate kinase deficiency is one of the most common enzymatic defects of the erythrocyte. Hemolysis may occur predominantly in the spleen extravascular or in the vessels intravascular with intravascular hemolysis, why are serum haptoglobin levels are reduced. Defective red cell metabolism as in glucose6phosphate dehydrogenase deficiency and pyruvate kinase deficiency paroxysmal nocturnal hemoglobinuria pnh, sometimes referred to as marchiafavamicheli syndrome, is a rare, acquired, potentially lifethreatening disease of the blood characterized by complementinduced intravascular hemolytic anemia. Hemolytic anemia in animals circulatory system merck. Pyruvate kinase deficiency genetics home reference nih. Pyruvate kinase deficiency, often referred to as pkd, is a blood disorder in which the enzyme pyruvate kinase pk is limited.
Pyruvate kinase deficiency anemia is caused by defective red cell metabolism due to the deficiency of the enzyme pyruvate kinase. Pyruvate kinase is an enzyme found in red blood cells that helps change sugar in the blood glucose to energy when oxygen levels are low. Symptoms of pyruvate kinase deficiency, hemolytic anemia. Symptoms of pyruvate kinase deficiency, hemolytic anemia including 9 medical symptoms and signs of pyruvate kinase deficiency, hemolytic anemia, alternative diagnoses, misdiagnosis, and correct diagnosis for pyruvate kinase deficiency, hemolytic anemia signs or pyruvate kinase deficiency, hemolytic anemia symptoms. Pyruvate kinase is the enzyme involved in the last step of glycolysis. These 2 phase 1 randomized, placebocontrolled, doubleblind healthy. Hemolytic anemia knowledge for medical students and physicians. Hemolysis may be influenced by a the basic medium employed, b the kind of blood used, c the length of the incubation period, d the atmosphere anaerobiosis may result in a reduction of hemolysis, e location of the colonies on the plates, f. Pyruvate kinase pk deficiency is the most common cause of congenital non spherocytic chronic hemolytic anemia and is the result of an erythrocyte enzyme. Pyruvate kinase deficiency is an inherited disorder that affects red blood cells, which carry oxygen to the bodys tissues. Voice of the patient report pyruvate kinase deficiency.