ESPE Abstracts

Background: Congenital Central Hypoventilation Syndrome (CCHS) is a rare disorder of respiratory control resulting from heterozygous polyalanine repeat expansions within the Paired-Like Homeobox 2B (PHOX2B) gene. A hypoglycaemic seizure in a 4-year-old girl with CCHS, lead to a more detailed examination of glycaemic control in a cohort of children with CCHS.

Objective: To describe glucose homeostasis in children with CCHS.

Methods: An observational cohort study of glucose homeostasis in seven children (3 months to 12 years) with genetically confirmed CCHS was conducted. Glycaemic profiles were evaluated using a combination of continuous glucose monitoring (CGM), fasting studies and response to an oral glucose tolerance test (OGTT). CGM was also used to compare the effect of Diazoxide and dietary intervention in the patient who presented with a hypoglycaemic seizure.

Results: Hypoglycaemia was not elicited by fasting in any of the patients. Increased postprandial glycaemic variability was evident in all patients using CGM, with 7/7 demonstrating initial hyperglycaemia (plasma glucose concentration >7.8 mmol/l 1–2 hours post-prandially), followed by asymptomatic hypoglycaemia (plasma glucose concentration ≤2.8 mmol/l) in 2/7. OGTT demonstrated asymptomatic hypoglycaemia occurring at 120 mins in both patients selected on the basis of CGM-detected hypoglycaemia. A low Glycaemic Index (GI) dietary intervention and Diazoxide treatment both reduced the proportion of CGM readings <4 mmol/l, however Diazoxide also increased the proportion of readings in the hyperglycaemic range.

Conclusion: Glucose variability associated with autonomic dysfunction may be unrecognised in CCHS, particularly in children with more severe phenotypes. This report highlights the occurrence of hyperglycaemia as well as hypoglycaemia in CCHS. Given the challenges of recognising hypoglycaemia based on clinical symptomatology, the use of CGM may facilitate its identification allowing appropriate management. The observed normoglycaemia during fasting combined with increased post-prandial BGL variability is more consistent with dumping syndrome than persistent hyperinsulinism. Dietary modifications therefore may be more effective than Diazoxide in managing hypoglycaemia. The long-term consequences of dysregulated glucose homeostasis in this group are unknown.