Endocrine Abstracts

Background: Congenital central hypoventilation syndrome [CCHS] is a rare autosomal dominant condition due to mutations in the transcription factor PHOX2B. It is characterized by alveolar hypoventilation with symptoms of autonomic nervous system dysfunction. Hyperinsulinaemic hypoglycaemia (HH) due to glucose dysregulation caused by anomalous insulin secretion has been reported as a feature of CCHS. However, HH and glycaemic outcomes in the context of CCHS have not been characterised in longitudinal follow-up.

Aim: To describe the variable phenotype of glucose dysregulation and glycaemic outcomes in children with CCHS.

Methods: We report 5 children with mutation-positive CCHS diagnosed with HH over a 15 year period in a cohort from one out of two Congenital Hyperinsulinism Highly Specialised Services in the UK. We describe the initial presentation, the challenges in management and glycaemic outcomes in longitudinal follow-up.

Results: All patients were term infants diagnosed with CCHS in the neonatal period, due to PHOX2B mutations and required long-term ventilation by tracheostomy. HH was diagnosed at median age 204 days (range 36-594) with post-prandial hypoglycaemia (3/5 patients) and fasting hypoglycaemia (2/5 patients). One patient was treated with diazoxide monotherapy; one with diazoxide and overnight gastrostomy feeds; one with acarbose and two with gastrostomy/NGT feeds. Two patients who presented earlier in the 15-year observation period demonstrated a reduction in the severity of HH over time, leading to hypoglycaemia resolution at a median age of 4.97 years (range 4.45-5.5 years), while patients presenting later and younger at follow up continued to require treatment for hypoglycaemia. No PHOX2B genotype to glycaemic phenotype correlation was noted.

Conclusion: It is important to recognise that both fasting and post-prandial hypoglycaemia may occur in patients with CCHS due to PHOX2B mutations requiring treatment for HH. These children must be monitored closely for symptoms of hypoglycaemia and investigated for HH. Our case series highlights that diazoxide can be effective treatment. Hypoglycaemia tends to reduce in severity over time and glycaemic resolution may be achieved over several years.