Background Donohue Syndrome is the most severe form of the rare genetic severe insulin resistance syndromes caused by mutation in the insulin gene receptor (INSR) with a lifespan under 2 years mainly because of intercurrent infections.

Resulting from a homozygous or compound heterozygous mutations of the INSR (INSR; 19p13.3– p13.2). It associates severe growth retardation beginning prenatally, hyperinsulinism with hyperglycemia and dysmorphic features.We report this case due to the extreme rarity of the syndrome and to present its clinical, biological findings and the underlying genetics.

Case Report(s) The case is an Algerian female infant born to consanguineous parents via caesarian section at 37weeks gestation due to severe intrauterine growth restriction.

She was admitted in our department at 4months old showing septic signs (high fever, tachycardia) with severe growth stunt (over -7DS), lipoatrophy, cholestasis, abdominal distension and dysmorphic features: craniofacial abnormalities with elfin facies and large low set ears, hypertrichosis and clitoromegaly.

Laboratory results showed hyperinsulinism with high insulin, peptic C and fasting hypoglycemia; postprandial hyperglycemia ; cholestatic hyperbilirubinemia and low triglyceride and cholesterol levels. C-reactive protein was high.

This presentation suggested DS which was confirmed by finding of a homozygous deletion in 19 p13.2 encompassing exon 2 of INSR.

Antibiotics were immediately put and growth hormone therapy was initiated (0,35 mg/kg/d); unfortunately, 3 days later she died from apparent septicemia. Our patient had no opportunity for treatment with recombinant IGF-1.

Conclusion(s) Our case shows a classic presentation of DS, with a fatal prognosis. Treatment is only symptomatic and requires a multidisciplinary team. Recombinant IGF-1 shows promise but the benefit is yet to be established.

Majority of cases are found where consanguineous marriages prevail, thus genetic counseling and discouraging inbreeding should be done as preventive measures awaiting optimal treatment protocol.