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.