eMedicine Specialties > Pediatrics: General Medicine > Hematology

Pyruvate Kinase Deficiency: Differential Diagnoses & Workup

Author: Hassan M Yaish, MD, Professor of Pediatrics, University of Utah School of Medicine; Director of Hematology Services, Medical Director, Mountain States Hemophilia and Thrombophilia Treatment Center; Pediatric Hematologist/Oncologist, Department of Pediatrics, Primary Children's Medical Center
Contributor Information and Disclosures

Updated: Oct 6, 2009

Differential Diagnoses

Anemia, Acute
Pyruvate Carboxylase Deficiency
Anemia, Chronic
Pyruvate Dehydrogenase Complex Deficiency
Carnitine Deficiency
Thalassemia
Glycogen-Storage Disease Type III
Thalassemia Intermedia
Hemoglobin H Disease
Hydrops Fetalis

Other Problems to Be Considered

In the newborn with jaundice and anemia, immune hemolysis (eg, ABO or Rh incompatibility) is easily identified. A diagnosis of pyruvate kinase (PK) deficiency is favored based on a negative Coombs test result, blood group setups, and a peripheral blood film examination that demonstrates no spherocytes but reveals contracted shrunken and speculated red cells (echinocytes) of the pyruvate kinase deficiency (see Media file 3). A normal osmotic fragility may help to differentiate pyruvate kinase deficiency from hereditary spherocytosis.

Other congenital hemolytic anemias of the nonspherocytic type, hemoglobinopathies, and thalassemia must also be differentiated. Specific tests and family history may help in the differentiation. In older children, autoimmune hemolytic anemia may also manifest with similar symptoms and, therefore, must be considered in the differential diagnosis. A positive Coombs test result, the presence of spherocytes, and the absence of the typical pyruvate kinase–deficient cells on the peripheral blood film examination are the main features in differentiating the conditions.

Workup

Laboratory Studies

  • CBC count, differential blood counts, reticulocyte counts, a serum bilirubin level study, and peripheral blood film examination are the minimal tests required to guide the investigation of pyruvate kinase (PK) deficiency.
  • Normochromic, normocytic, or macrocytic anemia, together with reticulocytosis in the absence of blood loss, is suggestive of hemolysis.
    • A negative Coombs test result helps to exclude immune hemolysis.
    • An elevated direct bilirubin level in the presence of indirect hyperbilirubinemia is not unusual in individuals with pyruvate kinase (PK) deficiency and does not necessarily indicate cholestasis, primary liver disease, or biliary obstruction. This finding was attributed to the deficient liver pyruvate kinase (LPK), an isoenzyme that is usually deficient whenever the red cell pyruvate kinase is deficient because of the common origin of both enzymes (the PKLR gene).
    • A recent report described hypertriglyceridemia in a female aged 6 months with pyruvate kinase deficiency resolving with hypertransfusion regimen. After a splenectomy at age 18 months, she remained transfusion independent with normal serum triglyceride levels.8
  • Enzyme assay and, more recently, DNA analysis involving polymerase chain reaction or single-strand conformation polymorphism are available to confirm the diagnosis and to identify the carrier state, if necessary. However, the enzyme assay might not always be accurate. This inaccuracy is due to the typical selective removal of very deficient red cells from the circulation, leaving only normal cells. Furthermore, the pyruvate kinase activity is usually normal in white cells, platelets, and other tissues in the patient with pyruvate kinase deficiency hemolytic anemia; this may interfere with the enzyme assay.

Imaging Studies

  • Ultrasonography is occasionally required to document gallbladder stones, which are known to complicate all forms of hemolytic anemias.

Histologic Findings

  • As a result of the chronic hemolysis, a bone marrow examination reveals erythroid hyperplasia and active marrow.
  • Iron stores may also be increased.

More on Pyruvate Kinase Deficiency

Overview: Pyruvate Kinase Deficiency
Differential Diagnoses & Workup: Pyruvate Kinase Deficiency
Treatment & Medication: Pyruvate Kinase Deficiency
Follow-up: Pyruvate Kinase Deficiency
Multimedia: Pyruvate Kinase Deficiency
References
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References

  1. Dacie JV, Mollison PL, Richardson N, et al. Atypical congenital haemolytic anaemia. Q J Med. Jan 1953;22(85):79-98. [Medline].

  2. Diez A, Gilsanz F, Martinez J, et al. Life-threatening nonspherocytic hemolytic anemia in a patient with a null mutation in the PKLR gene and no compensatory PKM gene expression. Blood. Sep 1 2005;106(5):1851-6. [Medline].

  3. Ayi K, Min-Oo G, Serghides L, Crockett M, Kirby-Allen M, Quirt I. Pyruvate kinase deficiency and malaria. N Engl J Med. Apr 24 2008;358(17):1805-10. [Medline].

  4. Kedar PS, Warang P, Colah RB, Mohanty D. Red cell pyruvate kinase deficiency in neonatal jaundice cases in India. Indian J Pediatr. Nov 2006;73(11):985-8. [Medline].

  5. Raphael MF, Van Wijk R, Schweizer JJ, et al. Pyruvate kinase deficiency associated with severe liver dysfunction in the newborn. Am J Hematol. Nov 2007;82(11):1025-8. [Medline].

  6. Hilgard P, Gerkin G. Liver cirrhosis as a consequence of iron overload caused by hereditary non-spherocytic hemolytic anemia. World J Gastroenterol. Feb 2005;11(8):1241-4. [Medline].

  7. Finkenstedt A, Bianchi P, Theurl I, et al. Regulation of iron metabolism through GDF15 and hepcidin in pyruvate kinase deficiency. Br J Haematol. Mar 2009;144(5):789-93. [Medline].

  8. Rao A, Hulbert M, Wilson DB. Severe hypertriglyceridemia in an infant with red cell pyruvate kinase deficiency. Indian Pediatr. Apr 2007;44(4):303-5. [Medline].

  9. [Guideline] Cunniff C. Prenatal screening and diagnosis for pediatricians. Pediatrics. Sep 2004;114(3):889-94. [Medline]. [Full Text].

  10. Aizawa S, Kohdera U, Hiramoto M, et al. Ineffective erythropoiesis in the spleen of a patient with pyruvate kinase deficiency. Am J Hematol. Sep 2003;74(1):68-72. [Medline].

  11. Nathan DG, Oski FA. Hematology of Infancy and Childhood. 5th ed. Philadelphia, Pa: WB Saunders Co; 1998.

  12. Nathan DG, Oski FA, Sidel VW, Diamond LK. Extreme hemolysis and red-cell distortion in erythrocyte pyruvate kinase deficiency. II. Measurements of erythrocyte glucose consumption, potassium flux and adenosine triphosphate stability. N Engl J Med. Jan 21 1965;272:118-23. [Medline].

  13. Rennels M, King J, Ryall R, et al. Dosage escalation, safety and immunogenicity study of four dosages of a tetravalent meninogococcal polysaccharide diphtheria toxoid conjugate vaccine in infants. Pediatr Infect Dis J. May 2004;23(5):429-35. [Medline].

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  17. Valentine WE, Tanaka KR, Miwa S. A specific erythrocyte glycolytic enzyme defect (pyruvate kinase) in three subjects with congenital non-spherocytic hemolytic anemia. Trans Assoc Am Physicians. 1961;74:100-10. [Medline].

  18. Zanella A, Fermo E, Bianchi P, Valentini G. Red cell pyruvate kinase deficiency: molecular and clinical aspects. Br J Haematol. Jul 2005;130(1):11-25. [Medline]. [Full Text].

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  20. Zarza R, Pujades A, Garcia J, et al. [Molecular study of red cell pyruvate kinase deficiency in 15 patients with chronic hemolytic anemia. Group of Erythropathology of Hematology and hemotherapy Association of Spain (HHAS)]. Med Clin (Barc). May 8 1999;112(16):606-9. [Medline].

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Further Reading

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Keywords

pyruvate kinase deficiency, PK deficiency, PKD, congenital nonspherocytic hemolytic anemia type II, CNSHA type II, hereditary spherocytosis, HS, adenosine triphosphate, ATP, hemolysis, 2, 3-diphosophoglycerate, 2, 3-DPG, PK-deficient reticulocytes, bilirubin level, anemia, idiopathic thrombocytopenic purpura, ITP, immune hemolysis, anaerobic glycolytic pathway, lactate, hemoglobin-oxygen dissociation curve, splenectomy, hyperbilirubinemia, nonimmune hydrops fetalis, jaundice, splenomegaly, gallbladder stones, exercise tolerance, fulminating infections

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Contributor Information and Disclosures

Author

Hassan M Yaish, MD, Professor of Pediatrics, University of Utah School of Medicine; Director of Hematology Services, Medical Director, Mountain States Hemophilia and Thrombophilia Treatment Center; Pediatric Hematologist/Oncologist, Department of Pediatrics, Primary Children's Medical Center
Hassan M Yaish, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Michigan State Medical Society, and New York Academy of Sciences
Disclosure: Nothing to disclose.

Medical Editor

Gary R Jones, MD, Associate Medical Director, Clinical Development, Berlex Laboratories
Gary R Jones, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Pediatric Hematology/Oncology, and Western Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

James L Harper, MD, Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Assistant Clinical Professor, Department of Pediatrics, Creighton University; Director, Continuing Medical Education, Children's Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center
James L Harper, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Federation for Clinical Research, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Council on Medical Student Education in Pediatrics, and Hemophilia and Thrombosis Research Society
Disclosure: Nothing to disclose.

CME Editor

Helen SL Chan, MBBS, FRCP(C), FAAP, Senior Scientist, Research Institute; Professor, Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Canada
Helen SL Chan, MBBS, FRCP(C), FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Society of Hematology, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Chief Editor

Robert J Arceci, MD, PhD, King Fahd Professor of Pediatric Oncology, Professor of Pediatrics, Oncology and the Cellular and Molecular Medicine Graduate Program, Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine
Robert J Arceci, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Pediatric Society, American Society of Hematology, and American Society of Pediatric Hematology/Oncology
Disclosure: Nothing to disclose.

 
 
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