De novo variants in HK1 associated with neurodevelopmental abnormalities and visual impairment

Eur J Hum Genet. 2019 Jul;27(7):1081-1089. doi: 10.1038/s41431-019-0366-9. Epub 2019 Feb 18.


Hexokinase 1 (HK1) phosphorylates glucose to glucose-6-phosphate, the first rate-limiting step in glycolysis. Homozygous and heterozygous variants in HK1 have been shown to cause autosomal recessive non-spherocytic hemolytic anemia, autosomal recessive Russe type hereditary motor and sensory neuropathy, and autosomal dominant retinitis pigmentosa (adRP). We report seven patients from six unrelated families with a neurodevelopmental disorder associated with developmental delay, intellectual disability, structural brain abnormality, and visual impairments in whom we identified four novel, de novo missense variants in the N-terminal half of HK1. Hexokinase activity in red blood cells of two patients was normal, suggesting that the disease mechanism is not due to loss of hexokinase enzymatic activity.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Erythrocytes* / enzymology
  • Erythrocytes* / pathology
  • Female
  • Hereditary Sensory and Motor Neuropathy* / enzymology
  • Hereditary Sensory and Motor Neuropathy* / genetics
  • Hereditary Sensory and Motor Neuropathy* / pathology
  • Hexokinase* / genetics
  • Hexokinase* / metabolism
  • Humans
  • Infant
  • Male
  • Mutation, Missense*
  • Pedigree*
  • Retinitis Pigmentosa / enzymology
  • Retinitis Pigmentosa / genetics
  • Retinitis Pigmentosa / pathology


  • HK1 protein, human
  • Hexokinase

Supplementary concepts

  • Neuropathy, hereditary motor and sensory, Russe type