title: Phenotypic expression of primary hyperoxaluria: comparative features of types I and II.
abstract: BACKGROUND
  The primary hyperoxalurias are autosomal recessive disorders resulting from deficiency of hepatic alanine:glyoxylate aminotransferase (PHI) or D-glycerate dehydrogenase/glyoxylate reductase (PHII). Marked hyperoxaluria results in urolithiasis, renal failure, and systemic oxalosis. A direct comparison of PHI and PHII has not previously been available.
  
  
  METHODS
  Twelve patients with PHI and eight patients with PHII with an initial creatinine clearance of greater than or equal to 50 mL/min/1.73 m2 underwent similar laboratory evaluation, clinical management, and follow-up. Diagnosis of PHI and PHII was made by hepatic enzyme analysis (N = 11), increased urinary excretion of glycolate or glycerate (N = 7), or complete pyridoxine responsiveness (N = 2). Six PHI and five PHII patients had measurements of calcium oxalate crystalluria, urine supersaturation, and urine inhibition of calcium oxalate crystal formation.
  
  
  RESULTS
  PHI and PHII did not differ in age at the onset of symptoms, initial serum creatinine, or plasma oxalate concentration. Urine oxalate excretion rates were higher in PHI (2.19 +/- 0.61 mmol/1.73 m2/24 hours) than PHII (1.61 +/- 0.43, P = 0.04). Urine osmolality, calcium, citrate, and magnesium concentrations were lower in PHI than PHII (P = 0.001, P = 0.019, P = 0.0002, P = 0.03, respectively). Crystalluria scores and calcium oxalate inhibitory activity of the urine did not differ between PHI and PHII. Calcium oxalate supersaturation in the urine was less in PHI (7.3 +/- 1.9) compared with PHII (14.0 +/- 3.3, P = 0.002). During follow-up of 10.3 +/- 9. 6 years in PHI and 18.1 +/- 5.6 years in PHII, stone-forming activity and stone procedures were more frequent in PHI than PHII (P < 0.01 and P = 0.01, respectively). Four of 12 PHI compared with 0 of 8 PHII patients progressed to end-stage renal disease (P = 0.03).
  
  
  CONCLUSIONS
  The severity of disease expression is greater in type I primary hyperoxaluria than in type II. The difference may be due to greater oxalate excretion and lower concentrations of urine citrate and magnesium in patients with PHI compared with PHII.
authors.affiliation: Division of Nephrology, Mayo Clinic, Rochester, Minnesota 55905, USA. milliner.dawn@mayo.edu
authors.forename: D S
authors.initials: DS
authors.lastname: Milliner
authors.forename: D M
authors.initials: DM
authors.lastname: Wilson
authors.forename: L H
authors.initials: LH
authors.lastname: Smith
mesh_terms: D000293:Adolescent; D000328:Adult; D002118:Calcium / Q000652:urine; D002129:Calcium Oxalate / Q000037:antagonists & inhibitors; D002648:Child; D002675:Child, Preschool; D019343:Citric Acid / Q000652:urine; D003460:Crystallization; D005260:Female; D006801:Humans; D006959:Hyperoxaluria / Q000145:classification* / Q000150:complications / Q000235:genetics* / Q000652:urine; D007676:Kidney Failure, Chronic / Q000209:etiology; D008274:Magnesium / Q000652:urine; D008297:Male; D009994:Osmolar Concentration; D010070:Oxalates / Q000652:urine; D010641:Phenotype; D014545:Urinary Calculi / Q000209:etiology; D014556:Urine / Q000502:physiology
chemical_list: D010070:Oxalates; D002129:Calcium Oxalate; D019343:Citric Acid; D008274:Magnesium; D002118:Calcium