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Primary Hyperoxaluria Type 1 Test

Genes:
AGXT

Syndrome Information

Clinical Description

Patients with primary hyperoxaluria (PHO) type I have a defect in the liver-specific enzyme alanine-glyoxylate aminotransferase encoded by AGXT.  Patients accumulate oxalate, and calcium oxalate deposits lead to urolithiasis, nephrocalcinosis and ultimately renal failure.  Other organs may be damaged as well.  Age of onset can vary widely from the first year to the third decade of life. 

Inheritance Pattern

Autosomal Recessive

Genotype-Phenotype Correlation

Missense mutations may be associated with milder clinical and biochemical phenotypes

Test Information

Test Method

Next Generation Sequencing (NGS) of the coding regions and intron-exon boundaries of AGXT; Deletion/Duplication:  Dosage analysis by normalization of NGS read depth for AGXT; Sanger sequencing for potential fill in / confirmation 

This test is also available as part of one or more NGS panels for peroxisomal disorders

Clinical Utility

Identification of causative mutations in known or suspicious cases of PHO; rule-out in the presence of equivocal clinical presentation and/or biomarker profile; targeted carrier testing of relatives of proband; predictive prenatal testing when familial mutations are known.

Clinical Sensitivity

Primary hyperoxaluria is divided into two types.  By definition, type 1 is caused by defects in AGXT.  Sequence analysis alone will identify two AGXT mutations in >95% of patients with PHO type 1.  Deletions or duplications are expected to account for 2-4% of AGXT mutations.

Analytic Sensitivity

>99% for inherited single nucleotide and small insertion/deletion variants for the nucleotides evaluated; >99% for multi-exon deletions and >98% for single exon deletions; >90% for multi-exon duplications and >75% for single exon duplications. Lower limit of detection for single nucleotide variants: 25% allele frequency (>99% sensitivity).

Sample Requirements

3-6ml whole blood in EDTA (purple topped) tubes. (see Pediatric or Adult blood sample algorithms for additional information)

We prefer whole blood for all tests.

Turn Around Time

Approximately 4 weeks

Fee and CPT Codes

NGS Panel:  $2450 for routine testing
CPT Code:  81479

Special Considerations

We request that copies of the patient's biochemical analysis be submitted with the sample.

NGS panels for peroxisomal disorders.

INFORMED CONSENT from the patient is required prior to ordering a genetic test. The DNA Diagnostic Lab's consent is located on the second page of the requisition form. There is also a patient brochure, "Things Every Patient Should Know Before Consenting to a Genetic Test", available for download.