Stones, bones, and heredity

Dawn Milliner

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Genetic disorders of mineral metabolism cause urolithiasis, renal disease, and osteodystrophy. Most are rare, such that the full spectrum of clinical expression is difficult to appreciate. Diagnosis is further complicated by overlap of clinical features. Dent's disease and primary hyperoxaluria, inherited causes of calcium urolithiasis, are both associated with nephrocalcinosis and urolithiasis in early childhood and renal failure that can occur at any age but is seen more often in adulthood. Bone disease is an inconsistent feature of each. Dent's disease is caused by mutations of the CLCN-5 gene with impaired kidney-specific CLC-5 chloride channel expression in the proximal tubule, thick ascending limb of Henle, and the collecting ducts. Resulting hypercalciuria and proximal tubule dysfunction, including phosphate wasting, are primarily responsible for the clinical manifestations. Low-molecular-weight proteinuria is characteristic. Definitive diagnosis is made by DNA mutation analysis. Primary hyperoxaluria, type I, is due to mutations of the AGXT gene leading to deficient hepatic alanine-glyoxylate aminotransferase activity. Marked overproduction of oxalate by hepatic cells results in the hyperoxaluria responsible for clinical features. Definitive diagnosis is by liver biopsy with measurement of enzyme activity, with DNA mutation analysis used increasingly as mutations and their frequency are defined. These disorders of calcium urolithiasis illustrate the value of molecular medicine for diagnosis and the promise it provides for innovative and more effective future treatments.

Original languageEnglish (US)
Pages (from-to)27-30
Number of pages4
JournalActa Paediatrica, International Journal of Paediatrics
Volume95
Issue numberSUPPL. 452
DOIs
StatePublished - Jul 1 2006

Keywords

  • Dent's disease
  • Hypercalciuria
  • Hyperoxaluria
  • Oxalosis
  • Urolithiasis

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Fingerprint Dive into the research topics of 'Stones, bones, and heredity'. Together they form a unique fingerprint.

Cite this