Neurological aspects of hyperinsulinism-hyperammonaemia syndrome.
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.
Bahi-Buisson
Nadia
N
Department of Paediatric Neurology and Metabolic Diseases, Necker Children's Hospital, Paris V University, Paris, France. nadia.bahi-buisson@nck.aphp.fr
Roze
Emmanuel
E
Dionisi
Carlo
C
Escande
Fabienne
F
Valayannopoulos
Vassili
V
Feillet
François
F
Heinrichs
Claudine
C
Chadefaux-Vekemans
Bernadette
B
Dan
Bernard
B
de Lonlay
Pascale
P
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
D006160:Guanosine Triphosphate; D005969:Glutamate Dehydrogenase