Background: Alagille syndrome (ALGS) is an autosomal dominant genetic disorder, with highly variable phenotype affecting multiple organs. Commonly presents in infancy or early childhood as cholestasis. Mutations in the notch signaling pathway ligand (JAG1) or its receptor (NOTCH2) lead to ALGS. This pathway is important for the pancreatic development. However,no cases of ALGS with Congenital Hyperinsulinism (CHI) have been reported to date.
Aim: To report an atypical case of ALGS presented with CHI.
Case report: A full-term female infant, with birth weight of 2.78 kg, developed cholestatic jaundice and episodes of hypoglycaemia on day 3 of life. Further investigations confirmed CHI and started Diazoxide (5 mg/kg per day) along with Chlorothiazide (7 mg/kg per day). She had mild facial dysmorphism with bossed forehead, prominent nasal bridge and small chin. Microarray showed monosomy of 20p11.21p12.2 due to interstitial deletion of the short arm of chromosome 20, consistent with ALGS. The infant was discharged at 4 weeks of life on Diazoxide and 4 hourly bottle feeds. She was diagnosed with a cardiac murmur due to a patent ductus, which was subsequently closed by the age of 12 months. At six-months of age, she was noted to have hepatomegaly (2 cm) with mildly raised bilirubin appeared. Diazoxide was discontinued at the age of 1 year after self-weaning of the medications. She has been on regular follow-up visits upto the age of ten years without further episodes of hypoglycaemia or hyperglycaemia.
Conclusion: ALGS is a rare inherited disease with variable phenotypic expressions. To the best of our knowledge, this is the first case of ALGS diagnosed with CHI that was Diazoxide-responsive and resolved at 12 months of age. Further work is needed to understand the mechanism of CHI in ALGS and children should be screened for CHI if any concerns regarding hypoglycaemia.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology