Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2017) 51 P064 | DOI: 10.1530/endoabs.51.P064

Diabetes

Hyperinsulinism Hyperammonemia (HI/HA) syndrome due to GLUD1 mutation: Phenotypic Variations Ranging from Late Presentation to Spontaneous Resolution

Agnieszka Brandt1, Dinesh Giri2, Zoe Yung2, Mohammad Didi2 & Senthil Senniappan2

30 views


1Clinic of Pediatrics, Diabetology and Endocrinology, Medical University of Gdansk, Gdansk, Poland; 2Alder Hey Children’s Hospital, Liverpool, UK.


Introduction: The hyperinsulinism/hyperammonemia (HI/HA) syndrome is the second most common cause of hyperinsulinemic hypoglycaemia (HH), caused by activating mutations in GLUD1 [which encodes the mitochondrial enzyme glutamate dehydrogenase (GDH)].

Methods: We describe phenotypic variations in three patients from 3 non-related families with HI/HA syndrome due to GLUD1 mutation.

Results: Patient 1, a 10-year-old Caucasian female born to non-consanguineous parents, presented with persistent hypoglycaemia and seizures at 7 months of age. Subsequent investigations during hypoglycaemia showed an inappropriately raised plasma insulin concentration (80 pmol/l) with supressed ketones and fatty acids confirming the diagnosis of HH. She had persistently high serum ammonia concentration [90–100 μmol/l (normal <70 μmol/l)]. A protein load test demonstrated protein-sensitive HH. Diazoxide was commenced (5 mg/kg per day) with good response and anticonvulsants were weaned and discontinued. At 8 years of age, diazoxide was gradually weaned and stopped as some high blood glucose values were noted. A 20-hour controlled fast [off diazoxide] and an oral protein load test did not show any hypoglycaemia. She continues to remain free from seizures and hypoglycaemia. Patient 2, a 4-year-old Caucasian boy born to non-consanguineous parents, presented with seizures at 8 months of age requiring anticonvulsant medications. Initial investigations at local hospital did not suggest HH but further investigations during seizures at 4 years of age confirmed HH. Diazoxide (6 mg/kg per day) was commenced with a good response and he continues on anticonvulsants. Patient 3, an 11-year-old Caucasian girl born to Polish non-consanguineous parents with a history of transient neonatal hypoglycaemia, presented with absence seizures at 12 months of age. Further investigations confirmed HH with hyperammoninaemia and good response to diazoxide (10 mg/kg per day) was noted and she did not require anticonvulsants. The genetic analysis in all three patients confirmed GLUD1 mutation.

Conclusions: The cases highlight the highly variable presentation of HI/HA syndrome leading to diagnostic challenges. Mild persistent hyperammonemia and hypoglycaemia in patients presenting with seizures should suggest HI/HA syndrome. Diazoxide may help weaning anticonvulsants in some patients. We noted complete spontaneous resolution of HI/HA in one patient at the age of 8 years, which has not been previously reported in the literature.

Volume 51

45th Meeting of the British Society for Paediatric Endocrinology and Diabetes

British Society for Paediatric Endocrinology and Diabetes 

Browse other volumes

Article tools

My recent searches

No recent searches.

My recently viewed abstracts

No recent abstracts.