A Case of MODY 5 Exhibiting Acute Onset of Diabetic Ketoacidosis in Combination with Metabolic Alkalosis, Hypokalemia and Hypomagnesemia

Abstract

A 26-year-old Japanese male who had polydipsia and consumed 1 l of sugar-containing soft drinks daily was admitted to our hospital with diabetic ketoacidosis with alkalemia. He received standard treatment for DKA with insulin and iv fluids. His plasma C-peptide level remained low after the improvement of glycemic control. His GAD antibody titer was undetectable. He had nephropathy characterized by hypokalemic alkalosis, normotensive hyperreninemic hyperaldosteronism and hypomagnesemia. A renal clearance study revealed that administration of furosemide, but not thiazide, decreased the chloride reabsorption. These are characteristic of Gitelman's syndrome or type III Bartter's syndrome, and may be associated with his polydipsia, which provoked DKA with alkalemia. However, his SLC12A3 and CLCNKB were normal. An abdominal CT showed deletion of the dorsal pancreas and enlargement of the left renal pelvis without an obstruction of the urinary tract. A genetic analysis revealed that he had a heterozygous 1.3-MB deletion mutation on 17q12 involving HNF1B, so he was diagnosed with maturity-onset diabetes of the young type 5 (MODY 5). Because HNF-1β is expressed in human nephrons, mutations of the gene may induce hypokalemia and hypomagnesemia related to inappropriate renal loss. This is the first case of MODY 5 complicated with nephropathy and hypokalemic alkalosis, which resulted in the acute onset of diabetic ketoacidosis with alkalemia.