Genetic Roots of Refractory Hypomagnesemia: A Case of Severe Renal Magnesium Wasting

Introduction: HNF1B mutations are associated with a spectrum of autosomal dominant disorders affecting renal development and tubular function. Among these, Autosomal Dominant Tubulointerstitial Kidney Disease often presents with subtle electrolyte abnormalities. Hypomagnesemia due to renal magnesium wasting is a hallmark but frequently underrecognized clinical feature. Case Description: We report a case of a 46-year-old female with a long standing history of refractory hypomagnesemia that came to the clinic with symptoms of fatigue, weakness, muscle spasm and tremors requiring multiple admission for IV magnesium replacement. Medications used include Magnesium 400 mg twice per day. Vital signs showed blood pressure 110/70mmHg, heart rate 70 beat per minute and RR 16. Laboratory results revealed creatinine levels 0.7mg/dL, BUN:35 mg/dL, chloride 105 mmol/L, bicarbonate 24 mmol/L, potassium levels 3.8 meq, Magnesium 1.2 mg/dl, Urine Creatinine 57 mg/dl and Urine Magnesium 37.3 mg/dl. Fractional Excretion of Magnesium (FEMg) calculation revealed a value of 54.53 %, indicative of severe renal magnesium wasting. Renal ultrasound showed normal-sized kidneys without cysts or structural abnormalities. Given the unexplained hypomagnesemia and early-onset CKD, genetic testing was pursued, which identified a heterozygous pathogenic variant in the HNF1B gene. There was no family history of kidney disease, suggesting a possible de novo mutation. Further evaluation showed mild glycosuria and low- normal serum bicarbonate, consistent with tubulopathy. Discussion: This case underscores the phenotypic variability of HNF1B-related disorders and emphasizes the importance of genetic testing in patients with unexplained electrolyte disturbances and chronic kidney disease (CKD). HNF1B mutations can lead to progressive tubulointerstitial fibrosis even in the absence of overt structural kidney anomalies such as renal cysts, diabetes syndrome, and Maturity-Onset Diabetes of the Young type 5 .Early recognition may influence family screening and prognosis. Clinicians should maintain a high index of suspicion for HNF1B-related kidney disease in patients with unexplained hypomagnesemia, even in the absence of a family history or structural abnormalities. Genetic testing is essential for accurate diagnosis and appropriate management.