[article]
| Titre : |
eIF5A and hypusination-related disorders: literature review and case report of DOHH-related encephalopathy |
| Type de document : |
texte imprimé |
| Auteurs : |
Álvaro BELTRÁN-CORBELLINI, Auteur ; Adrián VALLS-CARBÓ, Auteur ; Rafael TOLEDANO, Auteur ; Irene GARCÍA-MORALES, Auteur ; Irene SÁNCHEZ-MIRANDA ROMÁN, Auteur ; Antonio GIL-NAGEL, Auteur |
| Langues : |
Anglais (eng) |
| Mots-clés : |
Humans Eukaryotic Translation Initiation Factor 5A Peptide Initiation Factors/genetics Male RNA-Binding Proteins/genetics Mixed Function Oxygenases/genetics Oxidoreductases Acting on CH-NH Group Donors/genetics Female Brain Diseases/genetics Child, Preschool Lysine/analogs & derivatives Dhps Dohh Developmental and epileptic encephalopathy Dravet syndrome Eif5a Eukaryotic translation factors Febrile seizures Fenfluramine Refractory epilepsy committee waived the need for approval regarding this case report. Consent for publication: Written consent for publication was obtained from the parents of the patient. Competing interests: ABC, RT, IGM, ISMR and AGN have received support from, and served as paid consultants for UCB Pharma. AVC has no conflicts of interest. |
| Index. décimale : |
PER Périodiques |
| Résumé : |
BACKGROUND: Eukaryotic initiation factor 5 A (eIF5A) and hypusination-related disorders (eIF5A-HRD) are recently described diseases caused by pathogenic heterozygous variants in the translation factor EIF5A or biallelic variants in the two enzymes involved in the post-translational synthesis of hypusine in the eIF5A precursor, deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH), necessary for its activation. We review the current knowledge regarding eIF5A-HRD, and report the case of the sixth and oldest known patient with DOHH-related disorder (DOHH-D), aiming to expand and discuss the molecular basis and the general and epilepsy phenotypes of this group of diseases. RESULTS: Literature review yielded one paper describing 7 individuals with eIF5A-related disorders (eIF5A-D), one reporting 5 subjects with DHPS-related disorders (DHPS-D) and one characterizing 5 individuals with DOHH-D. Main phenotypic features consisted of prenatal issues, hypotonia, dysmorphisms, microcephaly, moderate-severe neurodevelopmental disorders/intellectual disability and behavioral disorders. We report the case of a 24-years-old male with DOHH-D manifesting as Dravet-like syndrome. He displays microcephaly and neurodevelopmental delay with attention deficit with hyperactivity disorder, along with a happy demeanor. Basic language skills and ambulation capacity with crouch gait are preserved. Onset of epilepsy was at 8 months with refractory temperature-triggered hemiclonic seizures and status epilepticus, followed by nocturnal tonic-clonic seizures from adolescence. Fenfluramine was the most effective approach, reducing seizure intensity, duration and frequency, and contributing to cognitive and behavior improvements. No patient with eIF5A-D presented seizures. Taking our patient into account, 4/5 and 4/6 reported individuals with DHPS-D and DOHH-D, respectively, presented epilepsy. Seven out of 8 epilepsy patients debuted between 2 and 5 years, most of them presented developmental and epileptic encephalopathies or generalized epilepsies (5/8 with temperature or infection-triggered seizures), and 4/8 were refractory. We hypothesize that dysregulation of IQSEC2 and SHANK3, among other genes, might contribute to the eIF5A-HRD phenotype. CONCLUSIONS: eIF5A-HRD are recently described entities displaying neurodevelopmental disorders and microcephaly, and reported patients are scarce. More than 70% of DHPS-D and DOHH-D patients present epilepsy, 63% of them with temperature-triggered seizures. Valproic acid or fenfluramine may be effective. Rare homozygous or compound heterozygous missense variants in these genes should be screened in patients with encephalopathy and temperature-triggered seizures. |
| En ligne : |
https://dx.doi.org/10.1186/s11689-025-09649-x |
| Permalink : |
https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576 |
in Journal of Neurodevelopmental Disorders > 17 (2025)
[article] eIF5A and hypusination-related disorders: literature review and case report of DOHH-related encephalopathy [texte imprimé] / Álvaro BELTRÁN-CORBELLINI, Auteur ; Adrián VALLS-CARBÓ, Auteur ; Rafael TOLEDANO, Auteur ; Irene GARCÍA-MORALES, Auteur ; Irene SÁNCHEZ-MIRANDA ROMÁN, Auteur ; Antonio GIL-NAGEL, Auteur. Langues : Anglais ( eng) in Journal of Neurodevelopmental Disorders > 17 (2025)
| Mots-clés : |
Humans Eukaryotic Translation Initiation Factor 5A Peptide Initiation Factors/genetics Male RNA-Binding Proteins/genetics Mixed Function Oxygenases/genetics Oxidoreductases Acting on CH-NH Group Donors/genetics Female Brain Diseases/genetics Child, Preschool Lysine/analogs & derivatives Dhps Dohh Developmental and epileptic encephalopathy Dravet syndrome Eif5a Eukaryotic translation factors Febrile seizures Fenfluramine Refractory epilepsy committee waived the need for approval regarding this case report. Consent for publication: Written consent for publication was obtained from the parents of the patient. Competing interests: ABC, RT, IGM, ISMR and AGN have received support from, and served as paid consultants for UCB Pharma. AVC has no conflicts of interest. |
| Index. décimale : |
PER Périodiques |
| Résumé : |
BACKGROUND: Eukaryotic initiation factor 5 A (eIF5A) and hypusination-related disorders (eIF5A-HRD) are recently described diseases caused by pathogenic heterozygous variants in the translation factor EIF5A or biallelic variants in the two enzymes involved in the post-translational synthesis of hypusine in the eIF5A precursor, deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH), necessary for its activation. We review the current knowledge regarding eIF5A-HRD, and report the case of the sixth and oldest known patient with DOHH-related disorder (DOHH-D), aiming to expand and discuss the molecular basis and the general and epilepsy phenotypes of this group of diseases. RESULTS: Literature review yielded one paper describing 7 individuals with eIF5A-related disorders (eIF5A-D), one reporting 5 subjects with DHPS-related disorders (DHPS-D) and one characterizing 5 individuals with DOHH-D. Main phenotypic features consisted of prenatal issues, hypotonia, dysmorphisms, microcephaly, moderate-severe neurodevelopmental disorders/intellectual disability and behavioral disorders. We report the case of a 24-years-old male with DOHH-D manifesting as Dravet-like syndrome. He displays microcephaly and neurodevelopmental delay with attention deficit with hyperactivity disorder, along with a happy demeanor. Basic language skills and ambulation capacity with crouch gait are preserved. Onset of epilepsy was at 8 months with refractory temperature-triggered hemiclonic seizures and status epilepticus, followed by nocturnal tonic-clonic seizures from adolescence. Fenfluramine was the most effective approach, reducing seizure intensity, duration and frequency, and contributing to cognitive and behavior improvements. No patient with eIF5A-D presented seizures. Taking our patient into account, 4/5 and 4/6 reported individuals with DHPS-D and DOHH-D, respectively, presented epilepsy. Seven out of 8 epilepsy patients debuted between 2 and 5 years, most of them presented developmental and epileptic encephalopathies or generalized epilepsies (5/8 with temperature or infection-triggered seizures), and 4/8 were refractory. We hypothesize that dysregulation of IQSEC2 and SHANK3, among other genes, might contribute to the eIF5A-HRD phenotype. CONCLUSIONS: eIF5A-HRD are recently described entities displaying neurodevelopmental disorders and microcephaly, and reported patients are scarce. More than 70% of DHPS-D and DOHH-D patients present epilepsy, 63% of them with temperature-triggered seizures. Valproic acid or fenfluramine may be effective. Rare homozygous or compound heterozygous missense variants in these genes should be screened in patients with encephalopathy and temperature-triggered seizures. |
| En ligne : |
https://dx.doi.org/10.1186/s11689-025-09649-x |
| Permalink : |
https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576 |
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