Comprehensive Genotypic, Phenotypic, and Biochemical Characterization of Got2 Deficiency: A Progressive Neurodevelopmental Disorder With Epilepsy and Abnormal Movements

Comprehensive Genotypic, Phenotypic, and Biochemical Characterization of Got2 Deficiency: A Progressive Neurodevelopmental Disorder With Epilepsy and Abnormal Movements Publisher Pubmed

German HM ; Zaki MS ; Usmani MA ; Karagoz I ; Efthymiou S ; Abdelhamid MS ; Arabiyat HA ; Ghaffar A ; Shahzad M ; Van Bokhoven H ; Ahmed ZM ; Yaghini O ; Hosseini N ; Majidinezhad M Show All Authors

German HM
Zaki MS
Usmani MA
Karagoz I
Efthymiou S
Abdelhamid MS
Arabiyat HA
Ghaffar A
Shahzad M
Van Bokhoven H
Ahmed ZM
Yaghini O
Hosseini N
Majidinezhad M
Alavi S
Bosma M
Broeks MH
Turkdogan D
Suri M
Laura De Godoy L
Verhoevenduif NM
Riazuddin S
Gleeson JG
Alves C
Jans JJM
Riazuddin S
Houlden H
Maroofian R

Source: Genetics in Medicine Published:2025

Abstract

Purpose Glutamic-oxaloacetic transaminase (GOT), also known as aspartate aminotransferase, catalyzes the reversible transamination of oxaloacetate and glutamate to aspartate and α-ketoglutarate. Two isoforms, cytosolic (GOT1) and mitochondrial (GOT2), are integral to the malate-aspartate shuttle, a key regulator of intracellular redox homeostasis. Recently, 5 patients with biallelic variants in GOT2 were described, presenting with developmental and epileptic encephalopathy. Methods We report 11 additional patients with homozygous GOT2 variants, along with additional data from 4 previously reported patients. Through genetic, clinical, and biochemical analyses, we further characterize the phenotypic spectrum of GOT2 deficiency. Results Most patients exhibited progressive neurodevelopmental delay, severe to profound intellectual disability, infantile epilepsy, progressive microcephaly, and hypotonia evolving into spasticity with axial hypotonia. Dysmorphic features included narrow foreheads, broad nasal tips, and tall or pointed chins. Neuroimaging revealed 2 severity groups based on cerebral volume loss and myelination defects. Thinning of the corpus callosum and white matter abnormalities were common. Biochemical profiling identified low aspartate and high glycerol-3-phosphate in dried blood spots as potential screening markers. Patient fibroblast cells showed reduced serine and glycine biosynthesis, rescuable by pyruvate supplementation. Conclusion These findings expand the phenotypic spectrum of GOT2 deficiency, establish it as a cause of developmental epileptic encephalopathy, and propose novel biomarkers for diagnosis and treatment. © 2025 The Authors.

Style	Citing Format
MLA	German HM, et al.. "Comprehensive Genotypic, Phenotypic, and Biochemical Characterization of Got2 Deficiency: A Progressive Neurodevelopmental Disorder With Epilepsy and Abnormal Movements." Genetics in Medicine, vol. 27, no. 12, 2025, pp. -.
APA	German HM, Zaki MS, Usmani MA, Karagoz I, Efthymiou S, Abdelhamid MS, Arabiyat HA, Ghaffar A, Shahzad M, Van Bokhoven H, Ahmed ZM, Yaghini O, Hosseini N, Majidinezhad M, Alavi S, Bosma M, Broeks MH, Turkdogan D, Suri M, ... Maroofian R (2025). Comprehensive Genotypic, Phenotypic, and Biochemical Characterization of Got2 Deficiency: A Progressive Neurodevelopmental Disorder With Epilepsy and Abnormal Movements. Genetics in Medicine, 27(12), -.
Chicago	German HM, Zaki MS, Usmani MA, Karagoz I, Efthymiou S, Abdelhamid MS, Arabiyat HA, et al.. "Comprehensive Genotypic, Phenotypic, and Biochemical Characterization of Got2 Deficiency: A Progressive Neurodevelopmental Disorder With Epilepsy and Abnormal Movements." Genetics in Medicine 27, no. 12 (2025): -.
Harvard	German HM et al. (2025) 'Comprehensive Genotypic, Phenotypic, and Biochemical Characterization of Got2 Deficiency: A Progressive Neurodevelopmental Disorder With Epilepsy and Abnormal Movements', Genetics in Medicine, 27(12), pp. -.
Vancouver	German HM, Zaki MS, Usmani MA, Karagoz I, Efthymiou S, Abdelhamid MS, et al.. Comprehensive Genotypic, Phenotypic, and Biochemical Characterization of Got2 Deficiency: A Progressive Neurodevelopmental Disorder With Epilepsy and Abnormal Movements. Genetics in Medicine. 2025;27(12):-.
BibTex	@article{ author = {German HM and Zaki MS and Usmani MA and Karagoz I and Efthymiou S and Abdelhamid MS and Arabiyat HA and Ghaffar A and Shahzad M and Van Bokhoven H and Ahmed ZM and Yaghini O and Hosseini N and Majidinezhad M and Alavi S and Bosma M and Broeks MH and Turkdogan D and Suri M and Laura De Godoy L and Verhoevenduif NM and Riazuddin S and Gleeson JG and Alves C and Jans JJM and Riazuddin S and Houlden H and Maroofian R}, title = {Comprehensive Genotypic, Phenotypic, and Biochemical Characterization of Got2 Deficiency: A Progressive Neurodevelopmental Disorder With Epilepsy and Abnormal Movements}, journal = {Genetics in Medicine}, volume = {27}, number = {12}, pages = {-}, year = {2025} }
RIS	TY - JOUR AU - German HM AU - Zaki MS AU - Usmani MA AU - Karagoz I AU - Efthymiou S AU - Abdelhamid MS AU - Arabiyat HA AU - Ghaffar A AU - Shahzad M AU - Van Bokhoven H AU - Ahmed ZM AU - Yaghini O AU - Hosseini N AU - Majidinezhad M AU - Alavi S AU - Bosma M AU - Broeks MH AU - Turkdogan D AU - Suri M AU - Laura De Godoy L AU - Verhoevenduif NM AU - Riazuddin S AU - Gleeson JG AU - Alves C AU - Jans JJM AU - Riazuddin S AU - Houlden H AU - Maroofian R TI - Comprehensive Genotypic, Phenotypic, and Biochemical Characterization of Got2 Deficiency: A Progressive Neurodevelopmental Disorder With Epilepsy and Abnormal Movements JO - Genetics in Medicine VL - 27 IS - 12 SP - EP - PY - 2025 ER -

Style

Citing Format

MLA

German HM, et al.. "Comprehensive Genotypic, Phenotypic, and Biochemical Characterization of Got2 Deficiency: A Progressive Neurodevelopmental Disorder With Epilepsy and Abnormal Movements." Genetics in Medicine, vol. 27, no. 12, 2025, pp. -.

APA

German HM, Zaki MS, Usmani MA, Karagoz I, Efthymiou S, Abdelhamid MS, Arabiyat HA, Ghaffar A, Shahzad M, Van Bokhoven H, Ahmed ZM, Yaghini O, Hosseini N, Majidinezhad M, Alavi S, Bosma M, Broeks MH, Turkdogan D, Suri M, ... Maroofian R (2025). Comprehensive Genotypic, Phenotypic, and Biochemical Characterization of Got2 Deficiency: A Progressive Neurodevelopmental Disorder With Epilepsy and Abnormal Movements. Genetics in Medicine, 27(12), -.

Chicago

German HM, Zaki MS, Usmani MA, Karagoz I, Efthymiou S, Abdelhamid MS, Arabiyat HA, et al.. "Comprehensive Genotypic, Phenotypic, and Biochemical Characterization of Got2 Deficiency: A Progressive Neurodevelopmental Disorder With Epilepsy and Abnormal Movements." Genetics in Medicine 27, no. 12 (2025): -.

Harvard

German HM et al. (2025) 'Comprehensive Genotypic, Phenotypic, and Biochemical Characterization of Got2 Deficiency: A Progressive Neurodevelopmental Disorder With Epilepsy and Abnormal Movements', Genetics in Medicine, 27(12), pp. -.

Vancouver

German HM, Zaki MS, Usmani MA, Karagoz I, Efthymiou S, Abdelhamid MS, et al.. Comprehensive Genotypic, Phenotypic, and Biochemical Characterization of Got2 Deficiency: A Progressive Neurodevelopmental Disorder With Epilepsy and Abnormal Movements. Genetics in Medicine. 2025;27(12):-.

BibTex

@article{ author = {German HM and Zaki MS and Usmani MA and Karagoz I and Efthymiou S and Abdelhamid MS and Arabiyat HA and Ghaffar A and Shahzad M and Van Bokhoven H and Ahmed ZM and Yaghini O and Hosseini N and Majidinezhad M and Alavi S and Bosma M and Broeks MH and Turkdogan D and Suri M and Laura De Godoy L and Verhoevenduif NM and Riazuddin S and Gleeson JG and Alves C and Jans JJM and Riazuddin S and Houlden H and Maroofian R}, title = {Comprehensive Genotypic, Phenotypic, and Biochemical Characterization of Got2 Deficiency: A Progressive Neurodevelopmental Disorder With Epilepsy and Abnormal Movements}, journal = {Genetics in Medicine}, volume = {27}, number = {12}, pages = {-}, year = {2025} }

RIS

TY - JOUR
AU - German HM
AU - Zaki MS
AU - Usmani MA
AU - Karagoz I
AU - Efthymiou S
AU - Abdelhamid MS
AU - Arabiyat HA
AU - Ghaffar A
AU - Shahzad M
AU - Van Bokhoven H
AU - Ahmed ZM
AU - Yaghini O
AU - Hosseini N
AU - Majidinezhad M
AU - Alavi S
AU - Bosma M
AU - Broeks MH
AU - Turkdogan D
AU - Suri M
AU - Laura De Godoy L
AU - Verhoevenduif NM
AU - Riazuddin S
AU - Gleeson JG
AU - Alves C
AU - Jans JJM
AU - Riazuddin S
AU - Houlden H
AU - Maroofian R
TI - Comprehensive Genotypic, Phenotypic, and Biochemical Characterization of Got2 Deficiency: A Progressive Neurodevelopmental Disorder With Epilepsy and Abnormal Movements
JO - Genetics in Medicine
VL - 27
IS - 12
SP -
EP -
PY - 2025
ER -

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Abstract