Characterizing the neurological phenotype of the hyperinsulinism hyperammonemia syndrome.

Autor: Rosenfeld E; Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, 3500 Civic Center Boulevard, Philadelphia, PA, 19140, USA. rosenfelde@chop.edu.; Congenital Hyperinsulinism Center, Children's Hospital of Philadelphia, Philadelphia, PA, USA. rosenfelde@chop.edu.; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. rosenfelde@chop.edu., Nanga RPR; Center for Advanced Metabolic Imaging in Precision Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA., Lucas A; Penn Center for Neuroengineering and Therapeutics, University of Pennsylvania, Philadelphia, PA, USA., Revell AY; Penn Center for Neuroengineering and Therapeutics, University of Pennsylvania, Philadelphia, PA, USA., Thomas A; Behavioral Neuroscience Core, Center for Human Phenomic Science, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Thomas NH; Behavioral Neuroscience Core, Center for Human Phenomic Science, Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Department of Child and Adolescent Psychiatry and Behavioral Sciences, Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Roalf DR; Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Shinohara RT; Penn Statistics in Imaging and Visualization Center, Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.; Center for Biomedical Image Computing and Analytics, Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Reddy R; Center for Advanced Metabolic Imaging in Precision Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA., Davis KA; Penn Center for Neuroengineering and Therapeutics, University of Pennsylvania, Philadelphia, PA, USA.; Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., De León DD; Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, 3500 Civic Center Boulevard, Philadelphia, PA, 19140, USA.; Congenital Hyperinsulinism Center, Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Jazyk: angličtina
Zdroj: Orphanet journal of rare diseases [Orphanet J Rare Dis] 2022 Jun 25; Vol. 17 (1), pp. 248. Date of Electronic Publication: 2022 Jun 25.
DOI: 10.1186/s13023-022-02398-3
Abstrakt: Background: Hyperinsulinism hyperammonemia (HI/HA) syndrome is caused by activating mutations in GLUD1, encoding glutamate dehydrogenase (GDH). Atypical absence seizures and neuropsychological disorders occur at high rates in this form of hyperinsulinism. Dysregulated central nervous system (CNS) glutamate balance, due to GDH overactivity in the brain, has been hypothesized to play a role. This study aimed to describe the neurologic phenotype in HI/HA syndrome and investigate CNS glutamate levels using glutamate weighted chemical exchange saturation transfer magnetic resonance imaging (GluCEST MRI). In this cross-sectional study, 12 subjects with HI/HA syndrome had plasma ammonia measurement, self- or parent-completed neurocognitive assessments, electroencephalogram (EEG), and GluCEST MRI at 7 T performed. GluCEST MRI measures were compared to a historic reference population of 10 healthy adults.
Results: Subjects were five males and seven females with median age of 25.5 years. Seventy-five percent of subjects reported a history of neurodevelopmental problems and 42% had neurocognitive assessment scores outside the normal range. Fifty percent had interictal EEG findings of generalized, irregular spike and wave discharges. Higher variability in hippocampal GluCEST asymmetry (p = 0.002), and in peak hippocampal GluCEST values (p = 0.008), was observed in HI/HA subjects (n = 9 with interpretable MRI) compared to the healthy reference population (n = 10).
Conclusions: The high prevalence of abnormal neurocognitive assessment scores and interictal EEG findings observed highlights the importance of longitudinal neuropsychological assessment for individuals with HI/HA syndrome. Our findings demonstrate the potential application of GluCEST to investigate persistent knowledge gaps in the mechanisms underlying the unique neurophenotype of this disorder.
(© 2022. The Author(s).)
Databáze: MEDLINE
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