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Peroxisomal Beta-Oxidation Defects NGS Panel


Syndrome Information

Clinical Description

The majority of patients peroxisomal beta-oxidation defects have liver disease, brain malformations, developmental retardation, sensory deficits, and dysmorphic craniofacial features.  At least 15% of patients who have clinical features suggestive of Zellweger spectrum disorder and elevated plasma very long chain fatty acids actually have a single enzyme defect in one of the peroxisomal beta-oxidation enzymes.  HSD17B4 deficiency is the most common (about 80%), followed by ACOX1 deficiency (15-20%) and then more rarely SCP2 deficiency (<5%).  The majority of Zellweger spectrum disorder and peroxisomal beta-oxidation defect patients can be distinguished by comprehensive biochemical analyses in blood, urine and cultured fibroblasts.  If such comprehensive biochemical testing has not been performed, then molecular testing can be used to confirm the diagnosis. Copies of the patient's biochemical analysis are extremely helpful in result interpretation. 

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 the listed genesDeletion/Duplication:  Dosage analysis by normalization of NGS read depth for the listed genes; 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 highly suspicious cases of peroxisomal beta-oxidation defects based on clinical presentation and the blood biomarker profile; 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

This testing detects HSD17B4, ACOX1 and SCP2 defects in about >80%, <20% and <5% of patients with a peroxisomal beta-oxidation defect, respectively.  This analysis will identify two mutations in the same gene in >98% of patients.  There have been individual case reports of deletions/duplications in HSD17B4 and ACOX1, but no published case series. 

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 4-6 weeks

Fee and CPT Codes

NGS Panel:  $2601 for routine testing
CPT Code:  81479 x 3

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.