OMg! What Links Hypomagnesemia, Kidney Stones, and Arrhythmia

Introduction: Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is an autosomal recessive disease that usually presents during early childhood and is known to be caused by mutations of claudin-16 and claudin-19. We discuss an atypical presentation of an adult patient with kidney stones and hypomagnesemia with genetic testing remarkable for heterozygous mutation in claudin-16 (c235C>G). Case Description: 23 year old female with history of kidney stones presented to the ED with ventricular fibrillation cardiac arrest. After successful resuscitation, she recovered quickly with intact neurological function. Initial workup revealed low-normal magnesium of 1.7 mg/dL which dropped to 1.5 mg/dL during hospitalization despite 4g of intravenous magnesium per day in addition to oral supplementation. Admission labs were also significant for a calcium of 7.8 mg/dL, albumin of 3.7 mg/dL and serum creatinine of 1.02 mg/dL, which improved during hospitalization. Laboratory values prior to this admission were not available. Medication history was unrevealing for culprit medications, including loop or thiazide diuretics. Urine studies revealed a fractional excretion of magnesium at 16%. Patient was supplemented with magnesium and discharged. During outpatient follow up, a 24 hour urine collection was obtained. She was found to have hypocitraturia, however with a normal urine calcium. Genetic testing was obtained which was negative for pathogenic variants but positive for a variant of unknown significance; a c235C>G heterozygous mutation in claudin-16. Upon outpatient clinic follow up, she continued to require magnesium oxide supplementation, currently at 400mg twice daily, with a corresponding magnesium level of 1.8 mg/dL. Discussion: FHHNC has over 50 known mutations in the claudin-16 gene, and presents in early childhood leading to progressive kidney failure. Our adult patient had significant renal magnesium wasting during hospitalization that continued as an outpatient, and required ongoing supplementation. Although clinical history and urine magnesium studies were consistent with FHHNC, she did not have hypercalciuria or family history of kidney stones or kidney failure. As genetic testing has become more common in clinical practice, this case highlights the need to critically assess variants of uncertain significance and monitor for any potential clinical manifestations.