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  • Author: Sarah E Flanagan x
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Sommayya Aftab Department of Paediatric Endocrinology, Great Ormond Street Hospital, London, UK

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Diliara Gubaeva Department of Paediatric Endocrinology, Endocrinology Research Centre, Moscow, Russia

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Jayne A L Houghton The Genomics Laboratory, Royal Devon & Exeter NHS Foundation Trust, Exeter, UK

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Antonia Dastamani Department of Paediatric Endocrinology, Great Ormond Street Hospital, London, UK

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Ellada Sotiridou Department of Paediatric Endocrinology, Great Ormond Street Hospital, London, UK

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Clare Gilbert Department of Paediatric Endocrinology, Great Ormond Street Hospital, London, UK

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Sarah E Flanagan Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK

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Anatoly Tiulpakov Department of Paediatric Endocrinology, Endocrinology Research Centre, Moscow, Russia

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Maria Melikyan Department of Paediatric Endocrinology, Endocrinology Research Centre, Moscow, Russia

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Pratik Shah Department of Paediatric Endocrinology, Great Ormond Street Hospital, London, UK

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Background

Hyperinsulinism/hyperammonemia (HI/HA) syndrome is the second most common type of congenital hyperinsulinism caused by an activating GLUD1 mutation.

Objective

The aim of this study was to determine the clinical profile and long-term neurological outcomes in children with HI/HA syndrome.

Method

This study is a retrospective review of patients with GLUD1 mutation, treated at two centers in the UK and Russia, over a 15-year period. Different risk factors for neuro-developmental disorders were analysed by Mann–Whitney U test and Fisher’s exact P test.

Results

We identified 25 cases with GLUD1 mutations (12 males). Median age of presentation was 7 months (12 h–18 months). Hypoglycaemic seizures were the presenting feature in 24 (96%) cases. Twenty four cases responded to diazoxide and protein restriction whilst one patient underwent partial pancreatectomy. In total, 13 cases (52%) developed neurodevelopmental manifestations. Epilepsy (n = 9/25, 36%), learning difficulties (n = 8/25, 32%) and speech delay (n = 8/25, 32%) were the most common neurological manifestation. Median age of presentation for epilepsy was 12 months with generalised tonic-clonic seizures being the most common (n = 4/9, 44.4%) followed by absence seizures (n = 3/9, 33.3%). Early age of presentation (P = 0.02), diazoxide dose (P = 0.04) and a mutation in exon 11 or 12 (P = 0.01) were associated with neurological disorder.

Conclusion

HI/HA syndrome is associated with wide spectrum of neurological disorders. These neurological manifestations were more frequent in cases with mutations affecting the GTP-binding site of GLUD1 in our cohort.

Open access