title: Autosomal recessive renal proximal tubulopathy and hypercalciuria: a new syndrome.
abstract: BACKGROUND
  The best described primary inherited proximal tubulopathies include X-linked hypercalciuric nephrolithiasis (XLHN), caused by a mutation in the chloride channel gene CLCN5, and classic Fanconi's syndrome, the genetic basis of which is unknown. The aim of this study is to examine the clinical, biochemical, and genetic characteristics of a highly consanguineous Druze family with autosomal recessive proximal tubulopathy and hypercalciuria (ARPTH), a syndrome not reported previously.
  
  
  METHODS
  Three children (2 girls, 1 boy) of the family referred for evaluation of renal glycosuria and hypercalciuria and 10 of their close relatives were evaluated clinically and biochemically. All study participants underwent genetic analysis to exclude involvement of the CLCN5 gene.
  
  
  RESULTS
  Evaluation of the 3 affected children showed glycosuria, generalized aminoaciduria, hypouricemia, uricosuria, low molecular weight (LMW) proteinuria, and hypercalciuria in all 3 children and phosphaturia in 2 children. They had no metabolic acidosis or renal insufficiency. One affected girl had nephrocalcinosis. Two children had a history of growth retardation and radiological findings of metabolic bone disease. Parathyroid hormone and 1,25-dihydroxyvitamin D [1,25(OH)2Vit D] blood levels in affected children were normal. Unaffected family members examined had no renal tubular defects or LMW proteinuria. Genetic linkage analysis excluded cosegregation of the ARPTH phenotype with the CLCN5 locus.
  
  
  CONCLUSIONS
  ARPTH is a new syndrome characterized by nonacidotic proximal tubulopathy, hypercalciuria, metabolic bone disease, and growth retardation. It can be distinguished from XLHN by its autosomal recessive mode of inheritance and normal serum levels of calciotropic hormones, as well as the absence of LMW proteinuria in obligate carriers. The gene mutated in ARPTH remains to be identified.
authors.affiliation: Pediatric Nephrology Unit, Meyer Children's Hospital, Rambam Medical Center and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. danmag@tx.technion.ac.il
authors.forename: Daniella
authors.initials: D
authors.lastname: Magen
authors.forename: Lior
authors.initials: L
authors.lastname: Adler
authors.forename: Hana
authors.initials: H
authors.lastname: Mandel
authors.forename: Edna
authors.initials: E
authors.lastname: Efrati
authors.forename: Israel
authors.initials: I
authors.lastname: Zelikovic
mesh_terms: D001851:Bone Diseases, Metabolic / Q000150:complications; D002118:Calcium / Q000652:urine*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005808:Genes, Recessive; D008040:Genetic Linkage; D006030:Glycosuria, Renal / Q000150:complications; D006130:Growth Disorders / Q000150:complications; D006801:Humans; D008297:Male; D010375:Pedigree; D010641:Phenotype; D015499:Renal Tubular Transport, Inborn Errors / Q000097:blood / Q000150:complications / Q000235:genetics* / Q000652:urine; D013577:Syndrome
chemical_list: D002118:Calcium