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.

Abstract

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.

• Authors: S M van der Hoeven, C S van Woerden, J W Groothoff
• Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (Nephrol Dial Transplant) Vol. 27 Issue 10 Pg. 3855-62 (Oct 2012) ISSN: 1460-2385 [Electronic] England
• PMID: 22844106 (Publication Type: Journal Article)

Chemical References

• Transaminases
• Alanine-glyoxylate transaminase

Topics

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