Journal of Pediatric Endocrinology and Metabolism, vol.22, no.7, pp.669-674, 2009 (SCI-Expanded)
Donohue syndrome describes the clinical consequences of the most severe genetic loss of insulin receptor function. The cardinal features are severe linear growth impairment pre- and postnatally with abnormal glucose metabolism and a characteristic pattern of soft tissue overgrowth. We report a 5 day old neonate with refractory hyperglycemia and paradoxical hypoglycemia, severe intrauterine growth retardation, typical 'elfin' facies (hypertrichosis, large and low-set ears, broad nasal tip, flared nares, thick lips), reduced subcutaneous fat, distended abdomen, and enlarged external genitalia and nipples. Fasting serum insulin and C-peptide were severely elevated at >2,100 pmol/l and >2,331 pmol/l, respectively. In addition, hepatic, ovarian and renal enlargement was demonstrated by ultrasonography. The neonate died within two months secondary to hypoglycemia. Diplex PCR analysis of the insulin receptor gene revealed the neonate to be homozygous for deletion of exon 3. Both parents were heterozygous for this deletion but were metabolically healthy. As such a deletion has previously been reported in Israel, we suggest that it may show a founder effect in the Middle East. © Freund Publishing House Ltd.