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Disease Profile

Nonspherocytic hemolytic anemia due to hexokinase deficiency

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

-

ICD-10

D55.2

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Hexokinase deficiency hemolytic anemia

Categories

Blood Diseases; Congenital and Genetic Diseases

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]

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]

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.

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

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]

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]

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.

References

  1. Nonspherocytic hemolytic anemia due to hexokinase deficiency. Orphanet. December 2007; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=90031. Accessed 1/30/2013.
  2. 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. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2738711/. Accessed 1/29/2013.
  3. Hexokinase deficiency. European Network for Rare and Congenital Anaemias. 2013; https://www.enerca.org/anaemias/38/hexokinase-deficiency. Accessed 1/30/2013.
  4. 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.
  5. Pyruvate kinase deficiency. MedlinePlus. February 2, 2012; https://www.nlm.nih.gov/medlineplus/ency/article/001197.htm. Accessed 2/1/2013.
  6. Anemia, Hereditary Nonspherocytic Hemolytic. NORD. July 23, 2007; https://www.rarediseases.org/rare-disease-information/rare-diseases/byID/82/viewAbstract. Accessed 1/30/2013.

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