Primary hyperoxaluria type 1, a too often missed diagnosis and potentially treatable cause of end-stage renal disease in adults: results of the Dutch cohort

Nephrol Dial Transplant. 2012 Oct;27(10):3855-62. doi: 10.1093/ndt/gfs320. Epub 2012 Jul 27.


Background: Primary hyperoxaluria Type 1, an inherited disorder with increased endogenous oxalate production, leads to the development of urolithiasis, nephrocalcinosis and end-stage renal disease (ESRD). Contrary to the general belief that patients diagnosed during adulthood experience a relatively mild course of disease, we were confronted with several cases of ESRD caused by previously undiagnosed primary hyperoxaluria.

Methods: To study renal and patient survival in relation with genotype, age at onset of disease and therapeutic delay, we performed a nationwide search among all Dutch nephrologists and paediatric nephrologists.

Results: Of the 79 included patients, 38% was diagnosed at an adult age. ESRD was present at the time of diagnosis in 26% of paediatric diagnosed patients versus 52% of adult-diagnosed patients (P = 0.021). Homozygosity for the pyridoxine-responsive p.Gly170Arg or p.Phe152Ile genotype was found in 26% of paediatric diagnosed patients versus 68% of adult-diagnosed patients (P < 0.001). Of homozygous p.Gly170Arg or p.Phe152Ile patients, 48% developed ESRD at a median age of 37 years, compared with 48% in those with other mutations at a median age of 0.5 years (P < 0.001). Of the 16 patients found through family screening, 81% had a preserved renal function.

Conclusions: The high prevalence of pyridoxine-responsive genotypes and favourably prognosis of timely treatment warrant early diagnostic screening for primary hyperoxaluria Type 1 in patients with recurrent urolithiasis. This will preserve kidney function and prevent diagnosis of adult diagnosed patients in ESRD.

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Child
  • Child, Preschool
  • Cohort Studies
  • DNA Mutational Analysis
  • Delayed Diagnosis
  • Female
  • Genetic Association Studies
  • Humans
  • Hyperoxaluria, Primary / complications*
  • Hyperoxaluria, Primary / diagnosis*
  • Hyperoxaluria, Primary / epidemiology
  • Hyperoxaluria, Primary / genetics
  • Infant
  • Infant, Newborn
  • Kidney Failure, Chronic / etiology*
  • Male
  • Middle Aged
  • Netherlands / epidemiology
  • Transaminases / deficiency
  • Transaminases / genetics
  • Young Adult


  • Transaminases
  • Alanine-glyoxylate transaminase

Supplementary concepts

  • Primary hyperoxaluria type 1