Neurological aspects of hyperinsulinism–hyperammonaemia syndrome |
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| Authors: | Nadia Bahi‐Buisson MD PhD Emmanuel Roze MD PhD Carlo Dionisi MD Fabienne Escande MD Vassili Valayannopoulos MD François Feillet MD PhD Claudine Heinrichs MD |
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| Affiliation: | 1. Department of Paediatric Neurology and Metabolic Diseases, Necker Children’s Hospital, Paris V University;2. Department of Neurology, Salpêtrière Hospital, AP‐HP, Paris, France;3. Division of Metabolism, Bambino Gesù Children’s Hospital, Rome, Italy;4. Biochemistry and Molecular Biology Laboratory, Centre for Biology and Pathology, Centre Hospitalier Régional Universitaire de Lille;5. Department of Paediatric Neurology and Metabolic Diseases, Necker Children’s Hospital, Paris V University, Paris;6. Reference Centre for Genetic Disorders, INSERM U724 Paediatric Medicine Service, Children’s Hospital, University Hospital Brabois, Vandoeuvre les Nancy, France;7. Department of Paediatrics, University Children’s Hospital Reine Fabiola, Free University, Brussels, Belgium. |
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| Abstract: | Hyperinsulinism–hyperammonaemia syndrome (HHS) is a rare cause of congenital hyperinsulinism, due to missense mutations in the GLUD1 gene, resulting in glutamate dehydrogenase (GDH) overactivity. The aim of this study was to document the spectrum of neurological disturbances associated with HHS and to identify possible phenotype–genotype correlations. We retrospectively analyzed the neurological outcomes of 22 consecutive patients (12 males, 10 females) aged from 18 months to 40 years and diagnosed with HHS. We analyzed demographic and clinical features and neuroradiological, biochemical, and genetic findings. Fourteen patients had childhood‐onset epilepsy. Learning disability * was found in 17 patients. Two patients had pyramidal involvement and one had generalized dystonia. Seizures were observed in 11 of 19 patients with documented GLUD1 mutations, and nine of these 11 patients had a mutation in the guanosine triphosphate (GTP) binding site. Our data demonstrate that neurological disorders in HHS are more frequent than previously thought and might suggest that mutations in the GTP binding site of GDH could be associated with more frequent epilepsy. |
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