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Metabolite diagnosis of primary hyperoxaluria type 3

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Abstract

Background

Primary hyperoxaluria type 3 (PH3) is a recently described cause of childhood renal calculi. It results from mutations in the HOGA1 gene and most cases have been diagnosed after clinical ascertainment, exclusion of other genetic hyperoxalurias and mutation testing. Metabolite testing has not been widely applied but holds promise for the rapid screening and diagnosis of patients who are not specifically suspected to have PH3.

Case-Diagnosis/Treatment

Two cases presented with renal calculi. Urine metabolite testing by tandem mass spectrometry was performed as part of the routine diagnostic work-up for this condition. Both had significantly increased levels of the PH3 urine marker 4-hydroxyglutamate and related metabolites. The diagnosis of PH3 was confirmed by the finding of bi-allelic damaging HOGA1 mutations.

Conclusions

Urine screening by tandem mass spectrometry is a rapid, high-throughput test that can detect PH3 cases that may otherwise not be diagnosed.

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Abbreviations

PH3:

Primary hyperoxaluria type 3

HOG:

4-Hydroxy-2-oxoglutarate

4OHGlu:

4-Hydroxyglutamic acid

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Acknowledgements

We thank Robert Dunlop, Ava Mishra, Kai Mun Hong, Mary Eggington and John Odontiadis for their expert assistance with metabolite screening.

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Authors and Affiliations

  1. Department of Clinical Biochemistry, Princess Margaret Hospital for Children, Perth, Australia

    Lawrence Greed

  2. Department of Nephrology, Princess Margaret Hospital for Children, Perth, Australia

    Frank Willis

  3. Department of Nephrology, Monash Children’s Hospital, Melbourne, Australia

    Lilian Johnstone & Sharon Teo

  4. Department of Paediatrics, Monash University, Melbourne, Australia

    Lilian Johnstone

  5. Division of Pediatric Nephrology, Shaare Zedek Medical Center, Jerusalem, Israel

    Ruth Belostotsky & Yaacov Frishberg

  6. Victorian Clinical Genetics Services, Murdoch Children’s Research Institute, Melbourne, Australia

    James Pitt

  7. Department of Paediatrics, University of Melbourne, Melbourne, Australia

    James Pitt

Authors
  1. Lawrence Greed
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  2. Frank Willis
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  3. Lilian Johnstone
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  4. Sharon Teo
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  5. Ruth Belostotsky
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  6. Yaacov Frishberg
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  7. James Pitt
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Corresponding author

Correspondence to James Pitt.

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The authors declare that they have no conflict of interest.

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Greed, L., Willis, F., Johnstone, L. et al. Metabolite diagnosis of primary hyperoxaluria type 3. Pediatr Nephrol 33, 1443–1446 (2018). https://doi.org/10.1007/s00467-018-3967-6

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  • DOI: https://doi.org/10.1007/s00467-018-3967-6

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