Clinical Overlap and Diagnostic Challenges: Differentiating HNF1B Mutation Disease from Gitelman Syndrome

Introduction: Hepatocyte nuclear factor 1 beta (HNF1B) mutation disease, is a rare genetic disorder characterized by a range of clinical manifestations, such as development of renal cysts, chronic kidney disease, electrolyte imbalances, and early-onset diabetes mellitus. HNF1B mutations are relatively rare, with an estimated prevalence of less than 1 in 100,000 individuals. One of the significant challenges in diagnosing this disease is its clinical overlap with other disorders, such as Gitelman's syndrome. Both conditions can exhibit similar symptoms, including chronic hypomagnesemia and hypokalemia, making differentiation between them difficult. Case Description: A middle-aged female with no significant past medical history, has been evaluated for chronic hypomagnesemia and hypokalemia, initially assumed to be due to Gitelman's syndrome. She was hospitalized for labor induction. Physical exam and vitals were normal. Laboratory findings showed a magnesium level of 1.2mEq/L and a potassium level of 3.5mmol/L, despite daily supplements. Other electrolytes and creatinine were normal. Of note, prior abdominal imaging showed bilateral renal cysts. The patient was given Intravenous magnesium sulfate which failed to improve magnesium level. She had a successful delivery with no complications and was then discharged home. On follow-up visit at the nephrology clinic, a full workup showed a potassium level of 4.1 mmol/L, magnesium level of 1.3mEq/L, fractional excretion of magnesium of 12%, normal kidney function and calcium level. Therefore, a genetic testing was ordered and came back positive for a single heterozygous mutation of HNF1B consistent with a deletion in a whole gene. Given the association between HNF1B mutation and Maturity Onset Diabetes of the Young (MODY), diabetes screening was performed and results were normal. The patient and her daughter, who also had bilateral renal cysts, were then referred for genetic counseling. Discussion: This case highlights the importance of the diagnostic complexities of HNF1B mutation disease, particularly due to its symptomatic overlap with conditions like Gitelman's syndrome. Genetic testing plays a crucial role in differentiating these disorders, enabling more precise treatment and better patient outcomes.