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Alpha Methylacyl-CoA Racemase Deficiency Test

Genes:
AMACR

Syndrome Information

Clinical Description

Patients with alpha methylacyl-CoA racemase deficiency accumulate phytanic acid, pristanic acid and the bile acid intermediates THCA and DHCA.  Usually pristanic acid accumulation in plasma is more significantly elevated than phytanic acid.  Most reported patients have presented with a neurological, motor, and retinal phenotype in adulthood.  There is a case report of an earlier onset presentation associated with neonatal cholestasis.

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 AMACR; Deletion/Duplication:  Dosage analysis by normalization of NGS read depth for AMACR; 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 AMACR Deficiency;  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

Since so few cases of AMACR deficiency have been reported, clinical sensitivity is an estimate based on the biochemical profile of elevated plasma phytanic acid, pristanic acid, DHCA, THCA and a pristanic/phytanic acid ratio > 1.  This analysiswill identify two AMACR mutations in greater than 98% of patients with the aforementioned  biochemical profile and no clinical or biochemical evidence of another peroxisomal defect.

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

$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.