{'fraction_non_alphanumeric': 0.05153445280833816, 'fraction_numerical': 0.03821656050955414, 'mean_word_length': 5.063157894736842, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Spectrum of neuro-developmental disorders in children with congenital hyperinsulinism due to activating mutations in GLUD1.

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
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 analyzed by Mann-Whitney U test and Fisher exact p.


RESULTS
We identified 25 cases with GLUD1 mutations (12 males). Median age of presentation was 7 months (12 hours-18 months). Hypoglycaemic seizures were the presenting feature in 24 (96%) cases. 24 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 generalized 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) was 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.