Background: Costello syndrome may be associated with Hyperinsulinaemic Hypoglycaemia (HI), but this is usually a mild medically-responsive form.
Objective and hypotheses: To describe the clinical characteristics, biochemical findings and challenging management of a case of Costello syndrome with severe HI.
Method: Review of the patients medical records.
Results: Male, born to non-consanguineous healthy parents, at term with birth weight of −0.45 S.D. with good Apgar scores, after a pregnancy complicated with polyhydramnios. He developed hypoglycaemia, feeding intolerance and tracheomalacia since day 1 of life. Subsequently found to have failure to thrive, biventricular hypertrophy with pulmonary stenosis and gastroesophagic reflux disease with possible abnormal gastric emptying, requiring gastrostomy feeds. The phenotype includes weight and height on the 0.4th centile, macroglossia, low set ears, deep palmar and plantar creases and abdominal distension (normal genitalia). Hypoglycaemia persisted despite continuous feeds and investigations were consistent with HI, with no hypoglycaemia being triggered by protein load or oral glucose tolerance test. Genetics were negative for the known HI, BWS, PTPN11 genes and a novel de novo mutation was found in the HRAS gene. He was tried on diazoxide, chlorothiazide, octreotide and sirolimus without achieving glycaemic control, hence a 95% pancreatectomy was performed which did not identify histologically abnormal pancreatic tissue. Despite surgery, hypoglycaemia persisted requiring the addition of octreotide injections to the continuous enteral feeds; unfortunately he developed tolerance to increased doses of octreotide. Aiming to avoid further surgery and considering the likelihood of increased insulin sensitivity, he was started on prednisolone (dose equivalent to 4 mg/m2 per day of hydrocortisone) combined with continuous feeds (8.2 mg/kg per min of glucose) achieving satisfactory blood glucose concentrations.
Conclusion: Costello can present with severe medically and surgically unresponsive HI. In view of possibly increased insulin sensitivity in some of these patients the use of steroids might help to avoid further surgery.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology