BSPED2008 Poster Presentations (1) (56 abstracts)
Hyperinsulinism--hyperammonaemia (HI/HA) syndrome: novel mutations in the GLUD1 gene and genotype phenotype correlations
R Kapoor 1 , S Flanagan 2 , J Shield 3 , A Chakrapani 4 , S Ellard 2 & K Hussain 1
1Institute of Child Health, London, UK; 2Peninsula Medical School, Exeter, UK; 3Bristol Children’s Hospital, Bristol, UK; 4Birmingham Children’s Hospital, Birmingham, UK.
Background: Hyperinsulinism–hyperammonaemia (HI/HA) syndrome is caused by gain of function mutations in the GLUD1 gene. Patients present with recurrent hyperinsulinaemic hypoglycaemia (HH) together with asymptomatic, persistent elevation of plasma ammonia levels. Leucine sensitivity is an important feature of this condition.
Objectives: The aim of this study was to understand the genotype phenotype correlations in patients with HH due to GLUD1 mutations and to report novel mutations.
Patients and methods: Fifteen unrelated patients with HI/HA had mutational analysis of the GLUD1 gene. In addition, one patient was analysed for a GLUD1 mutation in view of extreme protein sensitivity.
Results: Heterozygous missense mutations in 12/16 patients were detected, three of which were novel (N410D, D451V, P436L). Eleven of these patients had raised ammonia levels while one patient with a novel missense mutation P436L, had normal ammonia levels despite extreme leucine sensitivity. The patients with hyperammonaemia presented with seizures and seven of these have developed epilepsy. Four patients negative for a GLUD1 mutation have a mildly raised ammonia levels. The cause of HI/HA syndrome in these patients remains unknown.
Conclusion: Patients with the HI/HA syndrome may have a normal plasma ammonia level but still demonstrate leucine sensitivity. Hence testing for leucine sensitivity may be a more sensitive maker for HI/HA syndrome. There is a high risk of epilepsy in patients with HI/HA syndrome. Not all patients with HI/HA syndrome have mutations in the GLUD1 gene suggesting other possible genetic causes.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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