ESPE Abstracts

Introduction: Diazoxide is the first-line drug for Hyperinsulinemia-Hyperammonemia (HI/HA) syndrome, a disease due to a mutation in the glutamate dehydrogenase-1 (GLUD1) gene.Diazoxide, an opener of the pancreatic β-cells KATP-channels reducing insulin release, is uncommonly associated with thrombocytopaenia.

Aim: We describe a toddler with HI/HA syndrome who developed thrombocytopaenia on diazoxide treatment.

Subjects and methods: A 13-month-old boy was transferred to our department from a District Hospital (DGH) due to two episodes of tonic-clonic seizures associated with loss of consciousness, staring, hypoglycaemia (blood glucose (BG) 32mg/dl (1.7 mmol/l)). Treatment was intravenous (iv) Dextrose and oral feeds; continued to have asymptomatic hypoglycaemia (BG <60mg/dl (3.3 mmol/l)). On admission, he was alert, had normal physical examination and development, growth (15^th percentile). He was born at 39 weeks gestation, small for gestational age (birth weight 2210gr), first child of unrelated parents. His 28 year-old mother had epilepsy since the age of five years old, on antiepileptics; father 45 years old, healthy. Episodes of sweating, restlessness, and upper limbs tremor were reported the last four months prior to admission. Hypoglycaemia screen when BG 36mg/dl(2 mmol/l) revealed inappropriately high insulin and C-peptide levels (17,8μIU/ml and 3,3ng/ml respectively) with negative blood and urine ketones. Septic screen was negative, cortisol, thyroid function, growth hormone, metabolic screen, carnitine, acylcarnitine, imaging studies, electroencephalograph were normal. Hypoglycaemia and hyperammonaemia (92 mmol/l) were confirmed by a glucagon and protein-loading test leading to a suspected diagnosis of HI/HA syndrome. He was treated with iv dextrose 10%, oral feeds and oral diazoxide (max dose 6.7mg/kg/d) and hydrochlorothiazide (7 mg/kg/d). He responded well to medication and was discharged. He presented at the DGH on day 12 of diazoxide treatment with a two-day history of petechial rash and nose bleeds, no signs of infection. Platelet count (PLT) was 2K/μL (NR 150-450K/μL); treated with corticosteroids. On re-admission PLTs were 4K/μL; he received iv platelets, immunoglobulin, prednisolone, diazoxide was discontinued. On day 5 PLTs increased to 226K/μL, he had hypoglycaemic episodes. Diazoxide was replaced with octreotide and later with lanreotide. He has been well since with no hypoglycaemia +/- seizures, growth is on the 5^th centile; normal development.

Results: Genetic testing confirmed HI/HA syndrome to the patient and his mother. The thrombocytopaenia was ameliorated five days after diazoxide discontinuation (PLT 226 K/μL).

Conclusions: Diazoxide is a well-tolerated, oral medication for hyperinsulinaemic hypoglycaemia, thrombocytopenia is a rare side effect. In such cases, second-line treatment with other agents, such as octreotide, may be required.A full blood count should be obtained periodically.