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Nonspherocytic hemolytic anemia due to hexokinase deficiency (NSHA due to HK1 deficiency) is a very rare conditionmainly characterized by severe, chronic hemolysis, beginning in infancy. Approximately 20 cases of this condition have been described to date. Signs and symptoms of hexokinase deficiency are very similar to those of pyruvate kinase deficiency but anemia is generally more severe. Some affected individuals reportedly have had various abnormalities in addition to NSHA including multiple malformations, panmyelopathy, and latent diabetes.Itcan be caused by mutations in the HK1 gene and is inherited in an autosomal recessive manner. Treatment may include red cell transfusions for those with severe anemia.
Features include always present findings: Jaundice, Reduced erythrocyte hexokinase activity, and Nonspherocytic hemolytic anemia. 10 total HPO annotations.
Organ System | Phenotype Count | Example Features |
|---|---|---|
Blood and immune system | 5 | Increased immature red blood cells (reticulocytosis), Normochromic anemia, Enlarged spleen (splenomegaly) |
Digestive system | 3 | Cholelithiasis, Jaundice, Enlarged spleen (splenomegaly) |
Lab test results | 1 | Hyperbilirubinemia |
HK1 encodes hexokinase 1 (917 aa). Catalyzes the phosphorylation of various hexoses, such as D-glucose, D-glucosamine, D-fructose, D-mannose and 2-deoxy-D-glucose, to hexose 6-phosphate (D-glucose 6-phosphate, D-glucosamine 6-phosphate, D-fructose 6-phosphate, D-mannose 6-phosphate and 2-deoxy-D-glucose 6-phosphate, respectively). Highest expression in Brain Cerebellar Hemisphere (153.8 TPM) and Brain Cerebellum (139.0 TPM).
Non-spherocytic hemolytic anemia due to hexokinase deficiency is associated with mutations in the HK1 gene on chromosome 10.
The HK1 protein participates in HK1 H577_C672del, glucokinase and hexokinases, and Defective HK1 causes hexokinase deficiency (HK deficiency) pathways.
HK1 is classified as a druggable target (Enzyme and Kinase categories) with score 7.5.
Genetic testing for HK1 is available. Testing is considered confirmatory for diagnosis.
Biomarker and diagnostic research for non-spherocytic hemolytic anemia due to hexokinase deficiency has been reported in the published literature.
Phenotype severity distribution: 3 always present features.
Estimated prevalence: <1 in 1,000,000 (VERY_RARE).
No clinical trials have been registered for non-spherocytic hemolytic anemia due to hexokinase deficiency.
5 publications have been identified in PubMed for non-spherocytic hemolytic anemia due to hexokinase deficiency. Research spans Case Report / Case Series (60%), Diagnostic / Biomarker (20%), and Basic Science / Preclinical (20%).
Koleva L (2025). [PMID: 40943525](https://pubmed.ncbi.nlm.nih.gov/40943525/). *International journal of molecular sciences*. [Diagnostic / Biomarker]
Kilich G (2025). [PMID: 40862242](https://pubmed.ncbi.nlm.nih.gov/40862242/). *EJHaem*. [Case Report / Case Series]
Ukonmaanaho EM (2024). [PMID: 38415930](https://pubmed.ncbi.nlm.nih.gov/38415930/). *British journal of haematology*. [Case Report / Case Series]
Gök V (2024). [PMID: 38811201](https://pubmed.ncbi.nlm.nih.gov/38811201/). *British journal of haematology*. [Case Report / Case Series]
Bartnik M (2024). [PMID: 39766843](https://pubmed.ncbi.nlm.nih.gov/39766843/). *Genes*. [Basic Science / Preclinical]
Data assembled from 6 of 12 sources · Last updated Sep 20, 2026, 8:28 AM UTC
Online Mendelian Inheritance in Man
European rare disease database
Genetic and Rare Diseases Info Center