A familial syndrome due to Arg648Stop mutation in the X-linked renal chloride channel gene

Maurizio Bosio, Maria Luisa Bianchi, Sarah E. Lloyd, Rajesh V. Thakker

Research output: Contribution to journalArticlepeer-review


We describe a familial syndrome in two brothers who were investigated after the casual discovery of tubular proteinuria in their 1st month of life. During a follow-up of 20 and 11 years, respectively, the two children grew well and were asymptomatic, but developed the same biochemical abnormalities, i.e., tubular proteinuria and hyperphosphaturia, progressive decrease in serum phosphorus below the normal values for age, and an increase in serum 1,25-dihydroxyvitamin D levels over normal values. Moreover, hyperabsorptive hypercalciuria and systemic osteopenia developed and progressively worsened. In both children, at a different age, medullary nephrocalcinosis appeared. The oldest boy suffered a progressive decrease in urinary concentration ability and in glomerular filtration rate. Oral phosphate supplementation led to reversal of all biochemical abnormalities, with the exception of decreased phosphate tubular reabsorption and tubular proteinuria. With long-term phosphate supplementation, a normal bone mass was reached, while progression of nephrocalcinosis was arrested and impairment of renal function was slowed down. In a family study (siblings and parents), the only detectable abnormality was microglobinuria in the mother, thus suggesting a X-linked inheritance of this disorder. In the two probands a mutation within the renal chloride channel gene (CLCN5) was discovered.

Original languageEnglish
Pages (from-to)278-283
Number of pages6
JournalPediatric Nephrology
Issue number4
Publication statusPublished - May 1999


  • Chloride channel gene
  • Hypercalciuria
  • Microglobulinuria
  • Nephrocalcinosis
  • Osteopenia
  • Renal familial syndrome
  • Renal phosphate leak

ASJC Scopus subject areas

  • Nephrology
  • Pediatrics, Perinatology, and Child Health


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