ESPE Abstracts

Donohue syndrome(DS) is a rare and often lethal autosomal recessive disease. Its prevalence is estimated less than one in a million live births. Mutations in the insulin reseptor (INSR) gene cause rare severe INSR-related insulin resistance syndromes such as DS. It is characterized by severe insulin resistance (hyperinsulinemia, fasting hypoglycemia and postprandial hyperglycemia), intrauterine and postnatal growth retardation, hypotonia, organomegaly including heart, liver, kidneys and ovaries, developmental delay, hypertrichosis, reduced subcutaneous fat and prominent nipples. Patients with DS have typical facial dysmorphism with thick lips, broad nose, proptosis, large and low set ears. We report the case of surviving Turkish boy with DS who had typical facial dysmorphism, lipoatrophy, muscle wasting, nipple hypertrophy, macropenis and generalized hypertrichosis. Echocardiogram showed consentric left ventricular hypertrophy in his cardiological examination. He had homozygous mutation in exon 4 of the INSR gene (c.1049C>T / p.Ser350Leu). Both parents were found heterozygous for the mutant allele. There are currently no effective treatments for DS. Management aims to normalize blood glucose. Metformin treatment was started to normalize blood glucose (30 mg/kg/day initial dose) but discontinued at the first week due to the fasting hypoglycemia. During his follow-up, hyperglycemia exceeding 200 mg/dL was rarely observed and he had no hypoglycemia without treatment. Since his condition was stable, he was discharged from the hospital with frequent oral feeding at the second month of his life. At the last visit in our outpatient department, the patient was 16 -month old. His weight gain and height velocity were sufficient. His left ventricular hypertrophy didn’t get worse in monthly cardiological follow-up. Although our patient has a severe phenotype, on the contrary, he has a mild clinical course. This condition may be explained by the degree of insulin resistance and residual binding capacity. In conclusion, it is very important to perform preimplantation genetic diagnosis and provide genetic counseling to families with a risk of having an affected child with these syndromes. Identification of this mutation will help families planning future pregnancies and having healty children.