Abstract: SA-PO625
First Post-Natal Screening Study to Detect Primary Hyperoxaluria Types 1 and 3
Session Information
- Pediatric Nephrology - II
November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Pediatric Nephrology
- 1800 Pediatric Nephrology
Authors
- Martin Higueras, Cristina, German Hyperoxaluria Center, Bonn, Germany
- Beck, Bodo B., Uniklinik Koln, Koln, Germany
- Hohenfellner, Katharina, Kliniken der Stadt und des Landkreises Rosenheim GmbH, Rosenheim, Germany
- Hoppe, Bernd, German Hyperoxaluria Center, Bonn, Germany
Background
The three primary hyperoxalurias (PH) are ultra-rare diseases of the glyoxylate metabolism, at which three specific enzyme defects induce severe endogenous overproduction of oxalate, and thus its massively elevated urinary excretion. Clinical hallmarks are recurrent urolithiasis, progressive nephrocalcinosis and eventually end stage kidney failure. Early diagnosis should be mandatory to achieve better outcome, which is even more important now, as a new treatment option is available for type 1 primary hyperoxaluria.
Methods
After parents have signed informed consents, we include all routine new-born-screening cards send to our screening lab for testing the presence of the most common mutations of the AGXT (c.508G>A, PH 1) and HOGA1 (c700+5G>T, PH 3) genes in Europe, respectively. We expect to test > 150.000 samples. If patients are homozygous, treatment will be started promptly, and outcome will be compared to historical controls from the German PH registry (OxalGermany). If heterozygous mutations are found, repeated spot urine analysis is performed to exclude hyperoxaluria. In those new-borns with hyperoxaluria, further genetic analysis is done and, if being positive, they start treatment promptly.
Results
So far, we have screened 7131 newborns in the routine testing. Out of those, no patient with homozygous mutations for AGXT or HOGA1 have been found. However, we found 24 heterozygous patients each for AGXT and HOGA1 mutations, respectively. One other newborn was heterozygous for AGXT and HOGA1. In 19 (11 HOGA1, 8 AGXT) patients urine analysis is already available, all were normal for oxalate and PH-type specific metabolites.
Conclusion
This huge newborn screening program will answer multiple questions. First we can better calculate the true prevalence of two PH types in Germany, as genomic data supposes many more patients, as currently known. Secondly, we can promptly treat patients and prevent disastrous outcome. Thirdly, we will compare outcome of different treatments (standard with vitamin B6 compared to new RNAi, Oxlumo, in PH 1). Lastly, the batches of urine analyzed will provide best normative molar creatinine ratios not only for oxalate and related metabolites, but also for other lithogenic substances for the newborn period.
Funding
- Commercial Support –