ESPE Abstracts

Donohue Syndrome is a rare and lethal autosomal recessive disease caused by mutations in the insulin receptor gene. It presents severe insulin resistance, fasting hypoglycemia, post-prandial hyperglycemia, intrauterine and postnatal growth retardation, dysmorphic features, hypertrichosis. The diagnosis of Donohue syndrome was based on the clinical characteristics, laboratory evaluation and determination of the INSR mutation. We report a Turkish female patient with genetically proven Donohue syndrome who had hypertrophic cardiomyopathy.

Case: Our patient is the second child of healthy first degree consanguineous parents of Turkısh family. She was born at 36 weeks of gestation via caesarean section due to severe intrauterine growth retardation. She had hyperglycemia (328 mg/dl) with hyperinsulinemia (insulin: 5253 μIU/ml, C peptide: 76.16 ng/ml)in eighth day of hospitalization. Because of severe hyperglycemia iv insulin infusion was started at 0.01U/kg/h and progressively increased to 0.5 U/kg/h. In followed-up clinical time 2 U/kg/day insulin glargine added treatment and potentiated 15 U/kg/day. At the age of twenty five days she presented with cholestasis. Serum total bilirubin level was 8,93 gr/dl, direct bilirubin level was 6,8 gr/dl, serum aspartate transaminase was 265 U/L and serum alanine aminotransferase was 240 U/L. Molecular study found that the patient was homozygous deletion at exon 3-22 of the INSR gene. At the age of three months she admitted our hospital because of fasting hypoglycemia. During this admission, echocardiographic examination showed an increase of both inverventriculer septum and left ventricle posterior wall diameter. Septal thickness increased to 5.4 mm with left ventricular outflow tract obstruction and systolic anterior movement of the mitral valve. Treatment with propranolol was started. Recombinant ınsulin-like growth factor-I was not given because of risk for further cardiac hypertrophy. She was died at the age of 7 months because of respiratory insufficiency caused by a fulminant pulmanory infection.

Discussion: Our patient had a mild cardiac hypertrophy in later control echocardiograms. The data about the mechanism of myocardial hypertrophy in these patients is still conflicting. However, the most commonly accepted hypothesis is that myocardial hypertrophy is the result of the IGF-1activation which is also found in the heart caused by elevated insulin concentrations. Hypertrophic cardiomyopathy is frequently observed in Donohue syndrome and has high mortality. Therefore hypertrophic cardiomyopathy demands extra attention in Donohue syndrome. Treatment is generally hard and unsuccessful. Generally patients die in infantile period of life. So prenatal diagnosis and genetic counseling are quite important.