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

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 favourabl 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