Background: Prader-Willi syndrome (PWS), a neurogenetic disorder due to a lack of expression of paternal genes, clinical features include hypotonia, hypogonadism, impaired intellect, behavior disorder and hyperphagia with severe obesity. Impaired glucose tolerance and diabetes mellitus (DM) occur in 7-20% of patients with onset in late adolescence or adulthood. In this report, we describe a rare case of severe DM in a 9 year-old child with PWS.
Methods and Results: 10 years old male with PWS treated with metformin daily since one year presented with Hyperglycemia of 300-350 mg/dl and HBA1C of 13.5%. Laboratory tests revealed negative Anti GAD antibodies , elevated liver enzymes and hyperlipidemia; liver ultrasound showed steatohepatitis. OGTT and IVGTT indicated residual insulin secretion. The insufficientl response to increasing doses of Metformin, indicated the addition of basal and bolus insulin treatment. Statins treatment was initiated for Hyperlipidemia. The typically continuous weight gain in spite of the significant efforts to limit caloric intake as expected in PW patients complicated the metabolic control but the intensive therapy resulted in a decrease of 4% in HbA1C and improved liver function test and lipids profile.
Conclusion: This unique and unusual overt anti GAD negative diabetes presentation in a patient with PWS already at 9 years of age exerted a prominent therapeutic challenge. The severe hyperphagia complexed by cognitive limitations resulted in uncontrolled high carbohydrates consumption that could not be solved solely by oral hypoglycemic therapy. The possible beneficial effect of Growth hormone therapy in PWS (height gain, increase protein body mass) was challenged by worsening of hyperglycemia. Finally the unique early overt diabetes suggests that another dysfunctional co-player may be required for early overt disease.
