Bone Abstracts

Introduction: Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis is a rare autosomal recessive renal tubular disease caused by mutations in Claudin 16 and 19 genes, often complicated by progressive renal failure. We describe the clinical and genetic features and management of this condition in three patients at our centre.

Case 1: A 3-year-old south Asian boy with consanguinity presented with hypocalcemic seizures. Investigations revealed hypomagnesaemia and hypercalciuria with extensive nephrocalcinosis. Genetic studies confirmed homozygous inactivating mutation in the Claudin 16 gene. Over last 2.5 years he had stable renal function and normal blood pressure, and he remained on oral citrate and magnesium supplements, and hydrochlorothiazide. He has now developed hyperphosphatemia with secondary hyperparathyroidism and chronic kidney disease stage 2 (GFR 69, normal being >80), and needs 1α hydroxycholecalciferol with dietetic management for phosphate control.

Case 2: A 3-year-old white Caucasian girl with consanguinity presented with recurrent urinary tract infections, hematuria, and a large bladder stone requiring lithotripsy. Her investigations confirmed hypomagnesaemia with hypercalciuria and extensive nephrocalcinosis. Genetic studies revealed homozygous missense mutation in the Claudin 16 gene. Over last 4 years, she has remained well on oral magnesium and citrate supplements, and hydrochlorothiazide with normal blood pressure and renal function.

Case 3: A 9-month-old white Caucasian girl presented with two episodes of febrile convulsions. Investigations revealed profound hypomagnesaemia with normal other biochemical parameters. Urine calcium and magnesium levels were initially immeasurable. Once serum magnesium was normalised on oral magnesium supplements, she developed progressive hypercalciuria. Genetic studies show a heterozygous mutation in the Claudin 19 gene. Over last 9 months she has remained well with normal growth and development, and no vision problems. Her renal ultrasonography is currently normal; with normal blood pressure and renal function.

Conclusion: Mutations in the Claudin genes are known to cause hypomagnesaemia, hypercalciuria and progressive nephrocalcinosis due to paracellular absorption defects in the renal tubules. Long-term prognosis is poor with eventual renal failure requiring renal replacement therapy. Our experience suggests that children with this condition can have widely variable clinical presentation and progress. While Claudin 19 mutation is also associated with profound mental retardation and visual problems, the milder course in Case number three may be due to a heterozygous mutation that influenced the severity of the disease.