Recurrent Nephrolithiasis and Beyond: The Long Diagnostic Odyssey of a Case of CLDN16 Mutation

Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis (FHHNC) is a rare tubulopathy resulting from mutations in the CLDN16 and CLDN19 genes. The affected individuals commonly present with polyuria, polydipsia, excessive urinary magnesium (Mg) and calcium (Ca) wasting, nephrocalcinosis, nephrolithiasis, recurrent urinary tract infections, and renal dysfunction. We herein report a 22-year-old male born to consanguineous parents presenting with recurrent nephrolithiasis since early childhood. He gave a previous history of muscle cramps, tetany, and seizures on multiple occasions with reported hypocalcemia and hypomagnesemia. He had no ocular symptoms or any history of salt wasting. His family history is noncontributory. Laboratory parameters demonstrated persistent hypomagnesemia, hypercalciuria, secondary hyperparathyroidism, and mild renal impairment. Ultrasound and plain X-ray kidney-ureter-bladder (KUB) region illustrated bilateral nephrolithiasis and nephrocalcinosis. Genetic study identified a homozygous missense mutation in CLDN16 which correlates with the patient's clinical features. Mild renal dysfunction indicates that this patient may retain partial CLDN16 function. Treatment focused on high fluid intake with dietary changes along with potassium citrate and magnesium supplementation. FHHNC may go unnoticed during the evaluation of recurrent renal stones. Hence, this case report highlights the need for careful assessment of patients presenting with recurrent nephrolithiasis manifesting from an early age. Early distinction of the disease from other inherited tubulopathies may decelerate the progression of end-stage renal disease (ESRD) in FHHNC patients.