Implications of genotype and enzyme phenotype in pyridoxine response of patients with type I primary hyperoxaluria

Carla G. Monico, Julie B. Olson, Dawn S. Milliner

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Background: Marked hyperoxaluria due to liver-specific deficiency of alanine:glyoxylate aminotransferase activity (AGT) characterizes type I primary hyperoxaluria (PHI). Approximately half of PHI patients experience improvement in the degree of hyperoxaluria following pyridoxine (VB6) treatment. Recently, we showed an association between VB6 response and the commonest PHI mutation G170R, with patients possessing one or two copies showing 50% reduction or complete to near complete normalization of oxaluria, respectively. Two patients showed responses varying from this pattern. To further clarify the molecular basis of VB6 response in PHI, we performed additional genotyping. Methods: 23 PHI patients diagnosed via hepatic enzyme analysis, hyperoxaluria and hyperglycolic aciduria or homozygosity for a known mutation, availability of pre- and post-VB6 24-hour urine oxalate and GFR>40 ml/min/1.73 m2 were included. Data was retrieved retrospectively, oxalate measured by oxalate oxidase, and genotyping performed by PCR-based methods. Results: VB6 response was associated with the G170R and F152I mutations. Eight new sequence changes were detected. Conclusions: In PHI, two mutations resulting in AGT mistargeting are associated with VB6 response. Whether this favorable effect is specific to the peroxisomal-to-mitochondrial mistargeting caused by these changes or due to another mechanism remains to be determined.

Original languageEnglish (US)
Pages (from-to)183-186
Number of pages4
JournalAmerican Journal of Nephrology
Volume25
Issue number2
DOIs
StatePublished - Mar 2005

Fingerprint

Primary Hyperoxaluria
Pyridoxine
Hyperoxaluria
Genotype
Phenotype
Enzymes
Mutation
Oxalates
oxalate oxidase
Liver
Primary hyperoxaluria type 1
Urine
Polymerase Chain Reaction

Keywords

  • Genotype
  • Phenotype
  • Primary hyperoxaluria
  • Pyridoxine

ASJC Scopus subject areas

  • Nephrology

Cite this

Implications of genotype and enzyme phenotype in pyridoxine response of patients with type I primary hyperoxaluria. / Monico, Carla G.; Olson, Julie B.; Milliner, Dawn S.

In: American Journal of Nephrology, Vol. 25, No. 2, 03.2005, p. 183-186.

Research output: Contribution to journalArticle

Monico, Carla G. ; Olson, Julie B. ; Milliner, Dawn S. / Implications of genotype and enzyme phenotype in pyridoxine response of patients with type I primary hyperoxaluria. In: American Journal of Nephrology. 2005 ; Vol. 25, No. 2. pp. 183-186.
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