ABSTRACT
Objective To investigate the clinical features and disease-causing mutations of familial hypomagnesaemia with hypercalciuria and nephrocalcinosis.Methods In February 2016,a 24 year old female patient with left kidney stone and nephrocalcinosis in bilateral kidneys was admitted to our hospital.One month prior to this admission,she had been treated by PCNL to remove the most part of left kidney stone in otherhospital.Mter admission,She was found hypomagnesaemia (serum magnesium 0.65 mmol/ L) and hypercalciuria (24h urine calcium 364.0 mg) but with normal renal function (serum creatinine 101.5μmol/L).And the remained part of left kidney stone was removed by flexible ureteroscope.As she was considered probably with an autosomal recessive FHHNC,an analysis of CLDN16 and CLDN19 gene mutations was performed using her and her parents'peripheral white blood cells.Results Mutation analysis revealed this patient had two heterozygous mutations in the CLDN16.One is an one-base deletion mutation in the 123th codon in exon 2:368delA.The other is a missense mutation in the 139th codon in exon 2:416C →T which resulted in an amino acid change Ala139Val.Her parents respectively had one of each heterozygous mutation.In the six months follow-up,an oral administration with hvdrochlorothiazide,potassium citrate,and calcium magesium supplements significantly reduced her hypomagnesaemia (serum magnesiun 1.0 mmol/L) and hypercalciuria (24-h urine calcium 156.0 mg),and no stone recurrence and aggravation of nephrocalcinosis and renal dysfunction occurred.Conclusions We diagnosed a patient with FHHNC who had a novel compound heterozygous mutation of CLDN16.This rare disease should be suspected if there are three constant clinical features of hypomagnesaemia,hypercalciuria and nephrocalcinosis,and verified with CLDN16 and CLDN19 gene test.Currently the option for treatment of FHHNC is symptomatic treatment until severe deterioration of renal function.The hydrochlorothiazide,potassium citrate,and calcium magesium supplements may have considerable effects on hypomagnesaemia and hypercalciuria.