Nonspherocytic hemolytic anemia due to hexokinase deficiency

Title

Other Names:

Hexokinase deficiency hemolytic anemia

Categories:

Blood Diseases; Congenital and Genetic Diseases

Summary Summary

Nonspherocytic hemolytic anemia due to hexokinase deficiency (NSHA due to HK1 deficiency) is a very rare condition mainly characterized by severe, chronic hemolysis, beginning in infancy.^[1] Approximately 20 cases of this condition have been described to date.^[2] Signs and symptoms of hexokinase deficiency are very similar to those of pyruvate kinase deficiency but anemia is generally more severe.^[3] Some affected individuals reportedly have had various abnormalities in addition to NSHA including multiple malformations, panmyelopathy, and latent diabetes.^[4] It can be caused by mutations in the HK1 gene and is inherited in an autosomal recessive manner.^[2]^[1] Treatment may include red cell transfusions for those with severe anemia.^[3]

Last updated: 2/1/2013

Symptoms Symptoms

Hexokinase deficiency manifests itself primarily as nonspherocytic hemolytic anemia (NSHA).^[4] The signs and symptoms of hexokinase deficiency are very similar to those of pyruvate kinase deficiency, a more common inherited cause of hemolytic anemia, and may include jaundice, fatigue, lethargy, and pale skin.^[3]^[5]. However, the anemia associated with hexokinase deficiency is generally more severe.^[3]

There have been reports of some affected individuals having various other abnormalities including multiple malformations, panmyelopathy, and latent diabetes.^[4]

Last updated: 2/1/2013

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms	Other Names	Learn More: HPO ID
Percent of people who have these symptoms is not available through HPO
Abnormality of metabolism/homeostasis	Laboratory abnormality Metabolism abnormality [ more ]	0001939
Autosomal recessive inheritance		0000007
Cholecystitis	Gallbladder inflammation	0001082
Cholelithiasis	Gallstones	0001081
Congenital onset	Symptoms present at birth	0003577
Hyperbilirubinemia	High blood bilirubin levels	0002904
Jaundice	Yellow skin Yellowing of the skin [ more ]	0000952
Nonspherocytic hemolytic anemia		0001930
Normochromic anemia		0001895
Normocytic anemia		0001897
Reticulocytosis	Increased immature red blood cells Increased number of immature red blood cells [ more ]	0001923
Splenomegaly	Increased spleen size	0001744

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 2/1/2020

Do you have updated information on this disease? We want to hear from you.

Cause Cause

Nonspherocytic hemolytic anemia due to hexokinase deficiency has been shown to be caused by mutations in the HK1 gene, which cause at least a partial deficiency of the enzyme hexokinase.^[1]^[4] This enzyme plays an important role in the chemical processes involved in the breakdown of sugar molecules (glycolysis). Red blood cells depend on this process for energy; if an enzyme is defective in any one of the stages, the red blood cell cannot function properly and hemolysis takes place.^[6] When red blood cells cannot be replaced faster than they destroy themselves, anemia results.^[6]

Last updated: 2/1/2013

Inheritance Inheritance

Nonspherocytic hemolytic anemia due to hexokinase deficiency is inherited in an autosomal recessive manner.^[1] This means that a mutation in both copies of the gene associated with the condition must be present in order to be affected. The parents of an individual with an autosomal recessive condition each have one mutated copy of the gene in each cell and are referred to as carriers. Carriers typically do not have any signs or symptoms of the condition. When two carriers of the same autosomal recessive condition have children, each child has a 25% (1 in 4) risk to be affected, a 50% (1 in 2) risk to be an unaffected carrier like each parent, and a 25% risk to be unaffected and have 2 normal copies of the gene.

Last updated: 2/1/2013

Treatment Treatment

When severe anemia is present, blood transfusions may be necessary. Affected individuals should avoid any drugs that can cause destruction of red blood cells, as well as any environmental triggers that may be identified.^[6]

Last updated: 2/1/2013

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Nonspherocytic hemolytic anemia due to hexokinase deficiency. Click on the link to view a sample search on this topic.

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

I was diagnosed with this condition 25 years ago. I understand what the anemia is and how it affects my body but have not managed to find information about hexokinase deficiency in terms which I would understand. Can you give me any information about this please? See answer

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References References

Nonspherocytic hemolytic anemia due to hexokinase deficiency. Orphanet. December 2007; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=90031. Accessed 1/30/2013.
Karen M.K. de Vooght, Wouter W. van Solinge, Annet C. van Wesel, Sabina Kersting and Richard van Wijk. First mutation in the red blood cell-specific promoter of hexokinase combined with a novel missense mutation causes hexokinase deficiency and mild chronic hemolysis. Haematologica. September 2009; 94(9):1203–1210. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2738711/. Accessed 1/29/2013.
Hexokinase deficiency. European Network for Rare and Congenital Anaemias. 2013; http://www.enerca.org/anaemias/38/hexokinase-deficiency. Accessed 1/30/2013.
Rijksen G, Akkerman JW, van den Wall Bake AW, Hofstede DP, Staal GE. Generalized hexokinase deficiency in the blood cells of a patient with nonspherocytic hemolytic anemia. Blood. January 1983; 61(1):12-18.
Pyruvate kinase deficiency. MedlinePlus. February 2, 2012; http://www.nlm.nih.gov/medlineplus/ency/article/001197.htm. Accessed 2/1/2013.
Anemia, Hereditary Nonspherocytic Hemolytic. NORD. July 23, 2007; http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/82/viewAbstract. Accessed 1/30/2013.