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Invitae Primary Hyperoxaluria Panel

Test description

The Invitae Primary Hyperoxaluria panel analyzes 3 genes associated with primary hyperoxaluria, a disorder of glyoxylate metabolism associated with renal damage that may progress to kidney failure.

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Primary panel (3 genes)
  • Hyperoxaluria type I (AGXT)
  • Hyperoxaluria type 2 (GRHPR)
  • Hyperoxaluria type 3 (HOGA1)

The primary hyperoxalurias are inherited disorders of glyoxylate metabolism in which hepatic peroxisomal enzyme deficiencies result in excessive production of oxalate. The excess oxalate cannot be degraded and is excreted in large amounts by the kidneys, resulting in high urinary oxalate levels. Insoluble calcium oxalate crystals accumulate in the kidneys, leading to nephrolithiasis and nephrocalcinosis, which may progress to end-stage renal disease (ESRD) and systemic oxalosis (PMID: 1433562, 23334384).

Most patients present with signs or symptoms related to kidney stones. Kidney stones are present in 65% of patients before 10 years of age and in 85% before 20 years of age. A minority of patients present with failure to thrive and ESRD due to calcification of kidney tissue without discrete kidney stones. Recurring stones throughout childhood, adolescence, and adulthood are characteristic. Over time, however, progressive renal damage leads to reduced kidney function that can be evident as early as 4 months of age. In up to 30% of cases the diagnosis was not confirmed until patients reached end-stage renal failure (PMID: 22688746).

Effects on kidney function vary by type. Patients with PH1 showed a median age at progression to kidney failure of 33 years (PMID: 15961949, 20016466). Patients with PH2 and PH3 appear to have better outcomes, with a preservation of renal function in most of the cases.

This panel is estimated to identify pathogenic variants in at least 90% of patients with primary hyperoxaluria (PMID: 25644115).

Percent of PH Attributed to Pathogenic Variants by Each Gene
GENE %
AGXT 80
GRHPR 9
HOGA1 11

Primary hyperoxaluria is inherited in an autosomal recessive manner.

Primary hyperoxaluria is estimated to occur in 1 in 120,000 live births and prevalence of 1-3 per million population (PMID: 12543880, 16810517, 15961945).

This test may be appropriate for patients with:

  • Stones or nephrocalcinosis in infancy and childhood
  • Failure to thrive and ESRD in infancy or early childhood
  • Recurrent calcium oxalate stones or nephrocalcinosis in adults
  • Family history of primary hyperoxaluria
  • High levels of oxalate in urine or plasma

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
AGXT NM_000030.2
GRHPR NM_012203.1
HOGA1 NM_138413.3