Background: Leprechaunism (Donohue syndrome) is an extremely rare AR disease that presents with special phenotypic features including severe type of insulin resistance with high mortality in infancy.
Case study: R 3 ½ months old Syrian girl, born at 35 weeks of gestation with Asymmetrical IUGR. She developed hyperglycemia from day1 of life >150 mg/dl (350+/−60 mg/dl) and her serum insulin and c-peptide were very high (772 uU/ml and 29.9 ng/ml, respectively). Insulin infusion was started with requirement between 0.40.5 unit/kg/day to keep her BG < 200 mg/dl. After the first month, her insulin requirement decreased spontaneously and the insulin was stopped for 710 days three times (average BG =130+/−55 mg/dl despite the presence of severe hyperinsulinemia (1900 and 2875 uU/ml). By the second month, facial dysmorphism became obvious in the form of prominent eyes and maxilla, upturned nose, large and low set ears, thick lips, gum hyperplasia, long narrow face, thick eye brows hypertrichosis of the forehead and the back, long feet and button-like nipples. CGMS recorded average BG=350+/−100 mg/dl while off insulin with fluctuating levels (hypo- and hyperglycemia) and average BG =300+/− 50 mg/dl) while on insulin infusion. She was started on Metformin (50 mg PO aily), and her CGMS showed a reasonably good response to metformin with average BG of 150 mg/dl compared to BG on insulin. Continuous nasogastric feeding (NGT) with pancreatic enzyme replacement to prevent hypoglycemia was associated with weight gain. Genetic study revealed a peculiar autosomal recessive of INSR homozygous mutation (c.3583A>T p.Lys1195*). Both parents were carriers.
Discussion: We report a case of Donohue syndrome with a peculiar mutation. Using CGMS showed clearly her glycemic abnormalities and response to different therapies. Metformin was successful therapy that maintained BG in the normal range most of the times. She had exocrine pancreatic insufficiency (not described before in DS) that responded well to pancreatic enzyme replacement.
Conclusion: We described a cae of DS with peculiar genetic homozygous mutation of the INSR gene and some new phenotypic features (pancreatic insufficiency) and reasonable response to metformin therapy.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology