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. Pyruvate kinase deficiency an overview sciencedirect topics. Pyruvate kinase is an enzyme, or chemical, found within your red blood cells required to make energy. Deficiencies of most of the enzymes of the embdenmeyerhof glycolytic pathway, including pyruvate kinase pk, have been reported. 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.
This red blood cell breakdown is called hemolysis and pk deficiency is classified as a hemolytic anemia. When theres a shortage of the enzyme, the red blood cells wont be able. Pyruvate kinase deficiency causes, symptoms, diagnosis. 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. Hemolysis, myopathy, and cardiac disease associated with. Overview of hemolytic anemia hematology and oncology msd. Normal red blood cells erythrocytes have a lifespan of about 120 days. 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. 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. 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. Patients display a highly variable degree of severity. 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.
Additionally, decreased levels of plasma haptoglobin, a marker of rbc destruction, are evidenced1, 2, 3 regardless the site of hemolysis intravascular or extravascular. Symptoms of pyruvate kinase deficiency, hemolytic anemia. Infectious agents such as malaria and babesiosis invade red blood cells. Since pyruvate kinase deficiency is caused by a lack of the pyruvate kinase enzyme, a lower activity rate can confirm the diagnosis.
Hemolysis is a fundamental feature of sickle cell anemia that contributes to its pathophysiology and phenotypic variability. G6pd deficiency, pyruvate kinase deficiency, and others. Hemolytic anemia and pyruvate kinase deficiency in pregnancy. Pyruvate kinase deficiency an overview sciencedirect. Pyruvate kinase deficient hemolytic anemia in the northern. Pyruvate kinase, erythrocytes northwell health laboratories. One patient died, but the other two survived after an exchange transfusion. Learn vocabulary, terms, and more with flashcards, games, and other study tools. 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. Pyruvate kinase deficiency is a rare genetic disorder characterized by. Jul 01, 2012 background erythrocytic pyruvate kinase pk deficiency, first documented in basenjis, is the most common inherited erythroenzymopathy in dogs.
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. 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. Pyruvate kinase deficiency and related disorders of red cell. Animals labrador retrievers 2 siblings, 5 unrelated, pugs. A presumption of pyruvate kinase deficiency can then be confirmed through a blood test measuring the enzyme activity rate of the pyruvate kinase enzyme.
G6pd, pyruvate kinase deficiency hemoglobin synthesis disorders e. Check the full list of possible causes and conditions now. Hemolytic anemia is associated with complications that need monitoring, including the development of gallstones, iron overload and low bone density. 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. The clinical sequelae of intravascular hemolysis and. Safety and efficacy of mitapivat in pyruvate kinase deficiency. The intron sequences of the human ltype pyruvate kinase gene pklr were determined by using primers selected from the known cdna sequence.
Enzym defects g6pd deficiency, pyruvate kinase deficiency. Pyruvate kinase deficiency pkd symptoms and treatment. Phenotypically it exhibits a variable range of anemia, from mild to transfusiondependent. Autoimmune hemolytic anemia cancer therapy advisor. Pyruvate kinase deficiency genetics home reference nih. Without this crucial enzyme, the red blood cell breaks down more rapidly. Red blood cell pk deficiency is the most frequent enzyme disorder leading to chronic nonspherocytic haemolytic anaemia. Inheritance is mainly via autosomal recessive pattern, but autosomal dominant patterns have also been seen. For marked intravascular hemolysis, maintenance of renal perfusion and urine output is.
The signs and symptoms of the disease may vary greatly from person to person. It is the second most common cause of enzymedeficient hemolytic anemia. Hemolytic anemia is associated with complications that. Pyruvate kinase pk deficiency is an inherited autosomal. Lr gene mutations and a retrospective survey of pk mutations in a small and selected group of beagles and west highland white terriers whwt. Pyruvate kinase deficiency omim 266200 is one of the most common causes of hereditary nonspherocytic hemolytic anemia and is associated with lifelong chronic hemolysis. The deficiency of g6pd leads to hemolytic anemia in the face of oxidative stress see. Without this enzyme, red blood cells break down too easily, resulting in a low level of these cells hemolytic anemia. 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. Neonatal hemolytic jaundice is a risk factor for kernicterus. Pyruvate kinase pk deficiency is the most common cause of hereditary nonspherocytic hemolytic anemia. Patients affected with this chronic hemolytic anemia exhibit pale skin, jaundice, fatigue, dyspnea, and tachycardia.
These 2 phase 1 randomized, placebocontrolled, double. 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. If you have problems viewing pdf files, download the latest version of adobe reader. Jci intravascular hemolysis and the pathophysiology of. Diagnostic approach to hemolytic anemias in the adult. Pyruvate kinase deficiency nord national organization. Intravascular hemolysis and the pathophysiology of sickle cell disease article pdf available in journal of clinical investigation 1273. Surprisingly, however, the symptomatology is less severe than hematologic indices indicate. Start studying pyruvate kinase deficiency and hemolytic anemia. Pyruvate kinase pk deficiency is the most common cause of congenital nonspherocytic chronic hemolytic anemia and is the result of an erythrocyte enzyme. Common symptoms reported by people with pyruvate kinase deficiency anemia. 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, 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. Defects in pyruvate kinase pk and phosphofructokinase pfk, key regulatory enzymes in anaerobic glycolysis, result in impaired atp production and shortened erythrocyte survival. Pyruvate kinase deficiencies are seen in basenjis, beagles, west highland white terriers, cairn terriers, and other breeds, as well as abyssinian and somali cats. Pregnancy complicated by pyruvate kinase deficiency is rare. Pyruvate kinase pk deficiency is the most common cause of congenital nonspherocytic chronic hemolytic anemia and is the result of an. Pyruvate kinase converts phosphoenolpyruvate to pyruvate, creating 50% of the red cell total atp. 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. Pyruvate kinase pk is a key regulating enzyme of the glycolytic pathway involved in the production of atp metabolic energy. Hemolytic anemias are a group of conditions characterized by the breakdown of red blood cells. Hemolytic anemia in animals circulatory system merck. Red cell pyruvate kinase pk deficiency is the most frequent enzyme. Hemolytic anaemiaclassification hereditary intracorpuscular hemoglobinopathies hbs,thalassemias enzymopathies g6pd def. 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. Membranecytoskeletal defectshs, elliptocytosis, ovalocytosis,stomatocytosis aquired red cell membrane abnormalitypnh.
Congenital intrinsic hemolytic anemia from rbc enzyme defect. Diagnosis of pyruvate kinase deficiency pyruvate kinase. Erythrocytic pyruvate kinase mutations causing hemolytic. 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. Erythrocyte pyruvate kinase deficiency in nonspherocytic hemolytic anemia. Pyruvate kinase deficiency is an inherited lack of the enzyme pyruvate kinase, which is used by red blood cells. Pyruvate kinase was inappropriately named inconsistently with a conventional kinase before it was recognized that it did not directly. Oligonucleotide primers for these determined intron sequences were used to sequence the exons. Hemolytic anemia knowledge for medical students and. Erythrocytic pyruvate kinase mutations causing hemolytic anemia, osteosclerosis, and secondary hemochromatosis in dogs g. Electrophoretic, immunologic and kinetic characterization of erythrocyte pyruvate kinase in the basenji dog with pyruvate kinase deficiency. 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. 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.
Pyruvate kinase deficiency pkd is a rare genetic disorder characterized by the premature destruction of red bloods, which is called hemolytic anemia. Pyruvate kinase pk deficiency is a rare cause of neonatal hemolytic jaundice, with. 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 due to pyruvate kinase deficiency. 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. 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. 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. Defective red cell metabolism as in glucose6phosphate dehydrogenase deficiency and pyruvate kinase deficiency. Pyruvate kinase deficiency is an autosomal recessive disorder that is less. Philip lanzkowsky, in lanzkowskys manual of pediatric hematology and.
Pyruvate kinase deficiency is the second most common cause of enzymedeficient hemolytic anemia. Hemolysis can occur due to different causes and leads to the release of hemoglobin into the bloodstream. Glucose6phosphate dehydrogenase deficiency leads to. Genetic and rare diseases information center gard po box 8126, gaithersburg, md 208988126.
Hemolytic anemia knowledge for medical students and physicians. At that time, separate alleles or even genes at different loci were thought to be the possible bases for clinical variability. Red cell longevity is dependent on the atp produced in glycolysis fig. Pyruvate kinase deficiency is a chronic hemolytic anemia caused by mutations in pkr, a key glycolytic enzyme in erythrocytes.
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. Pyruvate kinase deficiency is an inherited metabolic disorder of the enzyme pyruvate kinase which affects the survival of red blood cells. Pyruvate kinase deficiency genetic and rare diseases. Pyruvate kinase deficiency is one of the most common enzymatic defects of the erythrocyte. Hemolytic anemia due to deficiency of erythrocytic pyruvate kinase is a rare autosomal recessive disorder. Pyruvate kinase deficiency anemia is caused by defective red cell metabolism due to the deficiency of the enzyme pyruvate kinase. Hemolysis may occur predominantly in the spleen extravascular or in the vessels intravascular with intravascular hemolysis, why are serum haptoglobin levels are reduced. 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 hematology medbullets step 1.
Voice of the patient report pyruvate kinase deficiency. Autosomal recessive mutation in the beta chain of hemoglobin. These 2 phase 1 randomized, placebocontrolled, doubleblind healthy. Concerned about the timing of jaundice and lack of any morphologic abnormalities, the pediatrician orders a functional assay to investigate pyruvate kinase. Three neonates with glucose6phosphate dehydrogenase g6pd deficiency are described. Pdf intravascular hemolysis and the pathophysiology of. Pyruvate kinase pk deficiency is the most common cause of congenital non spherocytic chronic hemolytic anemia and is the result of an. Without pyruvate kinase, red blood cells break down too easily, resulting in low levels of these cells hemolytic anemia. 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. 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. Massive acute haemolysis in neonates with glucose6phosphate.
Pyruvate kinase deficiency and hemolytic anemia quizlet. Both autosomal dominant and recessive inheritance have been observed with the disorder. Pyruvate kinase deficiency is an inherited disorder that affects red blood cells, which carry oxygen to the bodys tissues. Averys diseases of the newborn ninth edition, 2012. Molecular study of pyruvate kinase deficient patients with. When this technique was applied to the dna of 10 unrelated patients with pyruvate kinase deficiency, the following. Pk deficiency, although relatively rare, is the erythrocyte enzyme deficiency most frequently found to be a cause of chronic nonspherocytic hemolytic anemia cnsha. Dic, shock, renal failure, death chronic hemolysis. Red cell pyruvate kinase deficiency pkd is the most common glycolytic defect causing congenital non. Coagulation in the pathophysiology of hemolytic anemias. Disorders of red blood cell enzymes, membranes, and hemoglobin cause hereditary hemolytic anemias.
For language access assistance, contact the ncats public information officer. Red blood cells from heterozygous individuals possess only 40%60% of the pyruvate. Analysis of pyruvate kinasedeficiency mutations that. 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. Pyruvate kinase is the enzyme involved in the last step of glycolysis.
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. The disorder is characterized by lifelong chronic hemolysis of variable severity. Pyruvate kinase pk deficiency is a rare inherited form of anemia. Erythrocyte pyruvate kinase deficiency in nonspherocytic. Pyruvate kinase deficiency, often referred to as pkd, is a blood disorder in which the enzyme pyruvate kinase pk is limited. Properties of abnormal enzyme associated with hemolytic anemia in the basenji dog. Pdf pyruvate kinase deficiency and malaria gundula min. Pdf over the last several decades, our understanding of the genetic variation, pathophysiology, and complications of the hemolytic anemia. Pyruvate kinase deficiency with hemolytic anemia via the.