Severe Insulin Resistance and Recurrent Pancreatitis in an 18 year old with Alström Syndrome

Background: Alström syndrome (AS) is a rare autosomal recessive disorder caused by a mutation of ALMS1 gene. ALMS1 is located in primary cilia, which serve important sensory roles for the extracellular environment in virtually every organ. Insulin resistance is one of the earliest metabolic changes seen in individuals with AS; and progression of the disease tends to be accelerated. Case report: We describe an 18-year-old female with AS who experienced severe insulin resistance and recurrent pancreatitis. Despite good compliance and multiple combinations and dosing of insulin, including insulin pump therapy, her glycemic control remained inadequate. Over the past 5 years, she has been hospitalized 12 times for treatment of acute pancreatitis. Pancreatitis in AS seems to be related to severe hypertriglyceridemia, the latter caused by hyperphagia and insulin resistance. Discussion: Early onset of obesity with the multi-organ involvement characteristic of ALMS1 may explain the accelerated development and increased severity of insulin resistance. Defective function of ALMS1 also results in reduced numbers of GLUT4 receptors mobilized to adipose cell membranes when stimulated by insulin. Diet modifications and increased physical activity may be beneficial. Recurrent pancreatitis in AS seems to be related to hypertriglyceridemia. Conclusion: Early onset insulin resistance is characteristic of AS and can be severe. The expression of the ALMS1 mutation in the hypothalamus may contribute to hyperphagia, resulting in obesity. An elevated BMI is a significant risk factor for developing diabetes at a young age. A better understanding of the pathophysiology in this disease may help improve glycemic control and offer more effective treatment of multisystem disease in affected individuals.