91 -3 (89) 2026 - Khakimov D.P. - CASE REPORT: LEUKOENCEPHALOPATHY WITH DEVELOPMENTAL DELAY AND EPISODIC NEUROLOGIC REGRESSION (LEUDEN) ASSOCIATED WITH A MUTATION IN THE EIF2AK2 GENE

CASE REPORT: LEUKOENCEPHALOPATHY WITH DEVELOPMENTAL DELAY AND EPISODIC NEUROLOGIC REGRESSION (LEUDEN) ASSOCIATED WITH A MUTATION IN THE EIF2AK2 GENE

Khakimov D.P. - EMU University, Tashkent city

Resume

The article describes a clinical case of LEUDEN syndrome, an ultra-orphan genetic disorder caused by mutations in the EIF2AK2 gene, which encodes protein kinase R (PKR). Impairment of this protein's function leads to an inadequate integrated stress response (ISR), causing demyelination and neuronal death when exposed to stressors such as infections. The paper presents a clinical analysis of a patient born in 2020 (Uzbekistan) with significant psychomotor developmental delay, short stature (hypostature), and characteristic episodes of neurological regression following intercurrent infections (otitis, herpangina). Genetic testing using NGS revealed a likely pathogenic heterozygous variant c.674delC (p.S225Ffs5) in the EIF2AK2 gene. This case is the first described in the Uzbek population. The patient's clinical presentation (a combination of developmental delay, spasticity, and regression triggered by fever) aligns with global descriptions of the EIF2AK2-related disorder spectrum. Early diagnosis using whole-exome sequencing (WES) is critical for modifying management tactics. The primary strategy involves strict temperature control and infection prevention to forestall further progression of neurodegeneration.

Keywords: LEUDEN, EIF2AK2, leukoencephalopathy, neurologic regression, ultra-orphan diseases, integrated stress response.

First page

560

Last page

563

For citation:Khakimov D.P. - CASE REPORT: LEUKOENCEPHALOPATHY WITH DEVELOPMENTAL DELAY AND EPISODIC NEUROLOGIC REGRESSION (LEUDEN) ASSOCIATED WITH A MUTATION IN THE EIF2AK2 GENE//New Day in Medicine 3(89)2026 560-563 https://newdayworldmedicine.com/en/new_day_medicine/3-89-2026

List of References

1. Mao D, et al. De novo EIF2AK2 variants are associated with developmental delay, leukoencephalopathy, and neurologic decompensation. American Journal of Human Genetics. 2020;106(4):570–583. doi:10.1016/j.ajhg.2020.02.016.
2. Kuipers DJ, et al. EIF2AK2-related dystonia: A spectrum from isolated dystonia to complex neurological disease. Movement Disorders. 2021;36(5):1217–1228. doi:10.1002/mds.28462.
3. Online Mendelian Inheritance in Man (OMIM). Leukoencephalopathy, developmental delay, and episodic neurologic regression syndrome; LEUDEN. Entry No. 618877 [Internet]. 2023 [cited 2026 Mar 24]. Available from: https://omim.org/entry/618877
4. Orphanet. Early-onset generalized torsion dystonia / EIF2AK2 related. ORPHA:256 [Internet]. Available from: https://www.orpha.net/
5. ResearchGate. Recent clinical reviews on ISR (Integrated Stress Response) modulation in LEUDEN syndrome [Internet]. 2025–2026. Available from: https://www.researchgate.net/

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