Autosomal dominant HK1-related neurodevelopmental disorder with visual defects and brain anomalies (NEDVIBA) : An emerging mitochondrial disorder
(2025) In Genetics in Medicine Open 3.- Abstract
Purpose: Hexokinase 1 (HK1) encodes a ubiquitously expressed hexokinase, which is responsible for the first step of glycolysis, phosphorylation of glucose to glucose-6-phosphate. Both autosomal recessive and dominant variants in this gene have previously been shown to cause human disease, and presently, there are clinical data available for 27 individuals with the monoallelic neurodevelopmental disorder with visual defects and brain anomalies. Delineation of the entire phenotypic spectrum and genotype-phenotype relations will aid in management and counseling decisions. Methods: We present molecular and clinical data on 22 additional individuals with heterozygous, mostly de novo, variants in HK1. We also reviewed data from the published... (More)
Purpose: Hexokinase 1 (HK1) encodes a ubiquitously expressed hexokinase, which is responsible for the first step of glycolysis, phosphorylation of glucose to glucose-6-phosphate. Both autosomal recessive and dominant variants in this gene have previously been shown to cause human disease, and presently, there are clinical data available for 27 individuals with the monoallelic neurodevelopmental disorder with visual defects and brain anomalies. Delineation of the entire phenotypic spectrum and genotype-phenotype relations will aid in management and counseling decisions. Methods: We present molecular and clinical data on 22 additional individuals with heterozygous, mostly de novo, variants in HK1. We also reviewed data from the published literature. Results: The clinical manifestations of neurodevelopmental disorder with visual defects and brain anomalies include varying degrees of intellectual disability/developmental delay, hypotonia, epileptic encephalopathy, visual deficits, a Leigh syndrome spectrum pattern on brain magnetic resonance imaging, and elevated lactate in blood and cerebrospinal fluid, suggesting mitochondrial dysfunction. Based on severity, individuals can be classified into mild, moderate, severe, or lethal forms. In terms of genotype-phenotype correlation, we find that all individuals carrying a missense variant at the threonine 457 residue have severe clinical features. Conclusion: HK1 should be included in mitochondrial disorder gene sequencing panels.
(Less)
- author
- organization
- publishing date
- 2025-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Hexokinase, HK1, Leigh syndrome spectrum, Mitochondrial disorder, NEDVIBA
- in
- Genetics in Medicine Open
- volume
- 3
- article number
- 103425
- publisher
- Elsevier
- external identifiers
-
- pmid:40469904
- scopus:105004387611
- DOI
- 10.1016/j.gimo.2025.103425
- language
- English
- LU publication?
- yes
- id
- eb6af237-ae3a-4d01-b3cc-f9676fafcb56
- date added to LUP
- 2025-09-29 12:59:16
- date last changed
- 2025-09-30 03:00:07
@article{eb6af237-ae3a-4d01-b3cc-f9676fafcb56,
abstract = {{<p>Purpose: Hexokinase 1 (HK1) encodes a ubiquitously expressed hexokinase, which is responsible for the first step of glycolysis, phosphorylation of glucose to glucose-6-phosphate. Both autosomal recessive and dominant variants in this gene have previously been shown to cause human disease, and presently, there are clinical data available for 27 individuals with the monoallelic neurodevelopmental disorder with visual defects and brain anomalies. Delineation of the entire phenotypic spectrum and genotype-phenotype relations will aid in management and counseling decisions. Methods: We present molecular and clinical data on 22 additional individuals with heterozygous, mostly de novo, variants in HK1. We also reviewed data from the published literature. Results: The clinical manifestations of neurodevelopmental disorder with visual defects and brain anomalies include varying degrees of intellectual disability/developmental delay, hypotonia, epileptic encephalopathy, visual deficits, a Leigh syndrome spectrum pattern on brain magnetic resonance imaging, and elevated lactate in blood and cerebrospinal fluid, suggesting mitochondrial dysfunction. Based on severity, individuals can be classified into mild, moderate, severe, or lethal forms. In terms of genotype-phenotype correlation, we find that all individuals carrying a missense variant at the threonine 457 residue have severe clinical features. Conclusion: HK1 should be included in mitochondrial disorder gene sequencing panels.</p>}},
author = {{Ng, Bobby G. and Eklund, Erik A. and Rosenfeld, Jill A. and Elias, Abdallah F. and Abu-El-Haija, Aya and Bris, Celine and Barth, Magalie and Chae, Jong Hee and Choi, Murim and Dubbs, Holly A. and Fratter, Carl and Foulds, Nicola and Gamble, Candace and Gavrilova, Ralitza H. and Haven, Jaclyn and Hoffman, Trevor L. and Hunter, Jill V. and Larson, Austin and Lotze, Timothy Edward and Magoulas, Pilar and Magness, Emily C. and Bootin, Debra M. and Marsh, Eric D. and Nesbitt, Victoria and Pastore, Matthew T. and Poulton, Joanna and Rahman, Shamima and Scaglia, Fernando and Murali, Chaya and Posey, Jennifer and Rotenberg, Joshua and Schmalz, Betsy and Shinde, Deepali N. and Powis, Zöe and Sukenik-Halevy, Rivka and Truxal, Kristen V. and Uster, Tami and Machado Bressan Wilke, Matheus Vernet and Klee, Erik and Woo, Hyewon and Younkin, Donald and Zhao, Jianhua and Granadillo, Jorge and Lalani, Seema and Chitayat, David and Chung, Wendy K. and Freeze, Hudson H. and Okur, Volkan}},
keywords = {{Hexokinase; HK1; Leigh syndrome spectrum; Mitochondrial disorder; NEDVIBA}},
language = {{eng}},
publisher = {{Elsevier}},
series = {{Genetics in Medicine Open}},
title = {{Autosomal dominant HK1-related neurodevelopmental disorder with visual defects and brain anomalies (NEDVIBA) : An emerging mitochondrial disorder}},
url = {{http://dx.doi.org/10.1016/j.gimo.2025.103425}},
doi = {{10.1016/j.gimo.2025.103425}},
volume = {{3}},
year = {{2025}},
}