Identification of a SIRT1 mutation in a family with type 1 diabetes.

Type 1 diabetes is caused by autoimmune-mediated ß cell destruction leading to insulin deficiency. The histone deacetylase SIRT1 plays an essential role in modulating several age-related diseases. Here we describe a family carrying a mutation in the SIRT1 gene, in which all five affected members developed an autoimmune disorder: four developed type 1 diabetes, and one developed ulcerative colitis. Initially, a 26-year-old man was diagnosed with the typical features of type 1 diabetes, including lean body mass, autoantibodies, T cell reactivity to ß cell antigens, and a rapid dependence on insulin. Direct and exome sequencing identified the presence of a T-to-C exchange in exon 1 of SIRT1, corresponding to a leucine-to-proline mutation at residue 107. Expression of SIRT1-L107P in insulin-producing cells resulted in overproduction of nitric oxide, cytokines, and chemokines. These observations identify a role for SIRT1 in human autoimmunity and unveil a monogenic form of type 1 diabetes.

Gitelman's syndrome with persistent hypokalemia - don't forget licorice, alcohol, lemon juice, iced tea and salt depletion: a case report.

INTRODUCTION: Chronic hypokalemia is the main finding in patients with Gitelman's syndrome. Exogenous factors can trigger deterioration of the patient's condition and provoke clinical symptoms. We discuss the pathophysiology of and therapy for Gitelman's syndrome, with a focus on dietary factors which may aggravate the disease. CASE PRESENTATION: We describe the case of a 31-year-old, previously apparently healthy Caucasian Swiss man who presented to our hospital with gait disturbance of subacute onset and a potassium level of 1.5 mmol/L. A detailed medical history revealed that he had been consuming large amounts of licorice (in the form of Fisherman's Friend menthol eucalyptus lozenges). Despite discontinuing the intake of glycyrrhizinic acid, his potassium level remained low. Biochemical investigations showed refractory hypokalemia and secondary hyperaldosteronism, suggestive of Gitelman's syndrome. Despite treatment with supplementation of potassium and magnesium in combination with an aldosterone antagonist, further clinically symptomatic episodes occurred. Triggers could be identified only by repeated detailed history taking. In response to the patient's dietary excesses (ingestion of relevant amounts of alcohol, lemon juice and iced tea), his hypokalemia was aggravated and provoked clinical symptoms. Finally, vomiting and failure to replace salt led to volume depletion and hypokalemic crisis, with a plasma potassium level of 1.0 mmol/L and paralysis with respiratory failure necessitating not only infusion of saline and potassium but also temporary mechanical ventilation. CONCLUSION: Dietary preferences may have a much larger impact than any drug treatment on the symptoms of this chronic syndrome. Individual (mainly dietary) preferences must be monitored closely, and patients should be given dietary advice to avoid recurrent aggravation of hypokalemia with muscular weakness.