title: Neurological aspects of hyperinsulinism-hyperammonaemia syndrome.
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.
authors.affiliation: Department of Paediatric Neurology and Metabolic Diseases, Necker Children's Hospital, Paris V University, Paris, France. nadia.bahi-buisson@nck.aphp.fr
authors.forename: Nadia
authors.initials: N
authors.lastname: Bahi-Buisson
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Roze
authors.forename: Carlo
authors.initials: C
authors.lastname: Dionisi
authors.forename: Fabienne
authors.initials: F
authors.lastname: Escande
authors.forename: Vassili
authors.initials: V
authors.lastname: Valayannopoulos
authors.forename: François
authors.initials: F
authors.lastname: Feillet
authors.forename: Claudine
authors.initials: C
authors.lastname: Heinrichs
authors.forename: Bernadette
authors.initials: B
authors.lastname: Chadefaux-Vekemans
authors.forename: Bernard
authors.initials: B
authors.lastname: Dan
authors.forename: Pascale
authors.initials: P
authors.lastname: de Lonlay
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001921:Brain / Q000473:pathology; D001925:Brain Damage, Chronic / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004569:Electroencephalography; D004789:Enzyme Activation / Q000235:genetics*; D004831:Epilepsies, Myoclonic / Q000175:diagnosis / Q000235:genetics; D004832:Epilepsy, Absence / Q000175:diagnosis / Q000235:genetics; D004829:Epilepsy, Generalized / Q000175:diagnosis / Q000235:genetics; D004830:Epilepsy, Tonic-Clonic / Q000175:diagnosis / Q000235:genetics; D005260:Female; D005838:Genotype; D005969:Glutamate Dehydrogenase / Q000235:genetics*; D006160:Guanosine Triphosphate / Q000097:blood / Q000502:physiology; D006801:Humans; D022124:Hyperammonemia / Q000175:diagnosis / Q000235:genetics*; D006946:Hyperinsulinism / Q000175:diagnosis / Q000235:genetics*; D007003:Hypoglycemia / Q000175:diagnosis / Q000235:genetics*; D007223:Infant; D008099:Liver / Q000201:enzymology; D008279:Magnetic Resonance Imaging; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D009460:Neurologic Examination; D010179:Pancreas / Q000201:enzymology; D010641:Phenotype; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D006160:Guanosine Triphosphate; D005969:Glutamate Dehydrogenase