ESPE Abstracts

Introduction: Peroxisomal biogenesis disorders - Zellweger Syndrome Spectrum (PBD-ZWS) are rare disorders involving multiple systems including the central nervous system, adrenals, liver and skeleton but hyperinsulinism is not a recognized association. We present a child with PBD-ZWS due to a novel mutation in PEX1 who developed hyperinsulinaemic hypoglycaemia (HH).

Case report: A 7 month old boy presented with recurrent hypoglycemia. He was born at 41 weeks of gestation with a birth weight of 3.7 kg (0.48 SDS). He had bilateral sensorineural hearing loss, global developmental delay, hypotonia, visual delay, gastroesophageal reflux and liver dysfunction. Investigations showed inappropriately high insulin and low 3-hydroxybutyrate and fatty acid levels during hypoglycaemia suggestive of HH. Cortisol was low and a synacthen test confirmed adrenal insufficiency. The patient was treated with hydrocortisone (10mg/m2/day) and diazoxide (maximum dose 15 mg/kg/day) and the blood glucose stabilized. He was initially on parenteral nutrition, which was gradually transitioned on to oral feeds. Subsequently, diazoxide was gradually tapered and stopped and the blood glucose remained stable. At 10 months of age, he was able to fast for 10 hours without hypoglycaemia, with appropriately suppressed insulin at the end of the fast suggesting that HH was transient. His plasma very long chain fatty acids were elevated suggesting PBD-ZWS. Genetic analysis showed two heterozygous mutations in PEX1 [c.2097dupT p.(lle700TyrfsTer42) and c.1838G>A p.(Cys613Tyr)].

Conclusion: Transient diazoxide responsive HH can be associated with PBS-ZWS and occurred at an unusual age (7 months) in our patient.