Objectives: 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 and both hyperglycaemia as well as hyperinsulinaemic hypoglycaemia (HH) have been reported. Although the mechanism is unclear, autonomic dysfunction may underlie this dysregulation of glucose homeostasis.
Aim: To highlight the phenotype and treatment outcome of HH in children with CCHS.
Methods: We report three children diagnosed with CCHS and HH and the challenges of their management.
Results: All cases were term infants diagnosed with CCHS in the neonatal period and were found to have mutations in PHOX2B of which two were heterozygous for polyalanine repeat expansions (20/27). They presented with HH in infancy (range 30-80 days of life) with fasting hypoglycaemia; one case also demonstrated episodic post-prandial hypoglycaemia. All responded to diazoxide (ranging 5-11.3mg/kg/day), although the case with post-prandial hypoglycaemia also required overnight gastrostomy feeds. Two cases remain on diazoxide at 1.1 and 2.7 years, while a third case was gradually weaned off by 5.5 years. All three cases required long-term ventilation via tracheostomy had other characteristics of CCHS (Hirschsprung disease, autoimmune dysfunction) as well as other features (tracheomalacia, omphalocele, seizures).
Conclusion: Dysregulated glucose homeostasis may be an under-recognised in CCHS. Episodes of hypoglycaemia in children with CCHS could present either in response to fasting or postprandially. In contrast to a recent report, our cases of CCHS-associated HH exhibited predominantly fasting hypoglycaemia, which could be related to the severity of their CCHS based on mutation status (or maybe directly related to mutation). These children must be monitored closely for symptoms of hypoglycaemia and investigated for HH, including for post-prandial hypoglycaemia if any concerns. Our case series highlights that diazoxide can be effective treatment but sometimes-dietary intervention might be necessary.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology