X-linked recessive nephrolithiasis with renal failure

N Engl J Med. 1991 Sep 5;325(10):681-6. doi: 10.1056/NEJM199109053251003.


Background and methods: Nephrolithiasis may occur as a consequence of a number of hereditary disorders. We describe a large kindred from northern New York with hereditary nephrolithiasis accompanied by urinary concentrating defects, nephrocalcinosis, renal insufficiency, and renal wasting of potassium, phosphate, calcium, and uric acid. The pattern of inheritance was established by examining the patients and their records and interviewing family members. Selected members of the family were evaluated in detail, with measurements of erythrocyte cation fluxes and carbonic anhydrase (carbonate dehydratase) activity.

Results: The kindred consisted of 162 family members from six generations. All nine affected persons were male and appeared to have inherited the disease from their mothers. No affected man transmitted the gene to a son, but the daughters of affected men were carriers. The patients presented in childhood with calcium nephrolithiasis and proteinuria, with progression to nephrocalcinosis, urinary concentrating defects, and renal insufficiency. Renal biopsies revealed tubular atrophy, interstitial fibrosis, and glomerulosclerosis; the characteristic features of other forms of hereditary nephritis were absent. Abnormalities in the renal excretion of calcium, phosphate, potassium, and uric acid were found only in the adult members of the kindred, although renal biopsies were abnormal even in younger members. In one patient who has had a renal transplant for seven years, the disease has not recurred.

Conclusions: This kindred manifested an X-linked recessive nephrolithiasis with renal failure, a new form of hereditary renal disease. Most of the identifiable physiologic abnormalities occurred after the development of nephrolithiasis and renal insufficiency and may not be of pathogenetic importance.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Carbonic Anhydrases / metabolism
  • Child
  • Erythrocytes / metabolism
  • Female
  • Genes, Recessive*
  • Humans
  • Kidney / pathology
  • Kidney Calculi / complications
  • Kidney Calculi / genetics*
  • Kidney Calculi / pathology
  • Kidney Failure, Chronic / etiology
  • Kidney Failure, Chronic / genetics*
  • Kidney Failure, Chronic / pathology
  • Male
  • Middle Aged
  • Pedigree
  • X Chromosome*


  • Carbonic Anhydrases