A Case Study of Treatment-Resistant Hypomagnesemia in a Young Adult with HNF1B Mutation

Introduction: It is well-established that genetic mutations can cause familial hypomagnesemia syndromes. One of the most common inherited causes of renal malformation is mutation in the transcription factor hepatocyte nuclear factor 1B (HNF1B) which can result in renal tubular dysfunction, leading to magnesium wasting (1). HNF1B plays a role in the regulation of FXYD2 gene transcription, involved in the tubular handling of magnesium through encoding the γ a-subunit of the Na+-K+-ATPase. HNF1B is important in nephrogenesis and maintaining tubular function (2). In addition to these renal manifestations, HNF1B mutations have been linked to other clinical issues including exocrine pancreatic insufficiency, renal cysts, liver dysfunction, gout, and genital tract malformations (3). This high clinical variability can hamper clinical diagnosis. Case Description: We report a 35 year old female patient with a history of migraines, chronic hypokalemia, and hypomagnesemia presenting with refractory hypomagnesemia despite supplementation .She had several episodes of syncope and consistently low magnesium level ranging between 0.8-1.1 mmol/l for the past 7 months while on 8 tablets of magnesium supplementation (64 mg). Her potassium levels were normal with daily supplementation of 40 mEq. A 24-hour urinary magnesium test revealed hypermagnesuria and hypocalcuria. Genetic study revealed a whole gene deletion of HNF1B. Discussion: The patient's persistent hypomagnesemia raised concern for a genetic disorder affecting magnesium regulation. The presence of high magnesium and low calcium levels on a 24-hour urinary test further suggests this. Genetic analysis revealed a complete deletion of the HNF1B gene aligning with a diagnosis of HNF1B-related autosomal dominant tubulointerstitial kidney disease, a condition characterized by kidney cysts, diabetes, and issues with electrolyte regulation, including low magnesium and potassium levels. This case emphasizes the importance of considering genetic mutations in patients with stubborn hypomagnesemia and underscores the need for healthcare providers to refer such patients to a nephrologist or genetic counselor for thorough assessment. In summary, mutations in HNF1B are a common genetic cause of kidney malformations and tubular dysfunction. Identifying and addressing these related conditions are essential for providing optimal care to individuals with HNF1B syndrome.