Alpha-Methylacyl-CoA Racemase Deficiency (AMACR)

Alpha-Methylacyl-CoA Racemase (AMACR) deficiency is an uncommon disorder that is classified as an autosomal recessive peroxisomal disorder and is due to biallelic variants in the AMACR gene. Leveraging advanced technologies and expertise in rare disease research, Protheragen provides complete diagnostics and therapeutics development services for AMACR deficiency.

Overview of Alpha-Methylacyl-CoA Racemase Deficiency (AMACR)

Alpha-Methylacyl-CoA Racemase Deficiency (AMACR) is a metabolic ailment of the peroxisome caused by the toxic accumulation of bile acid intermediates and pristanic acid due to the organism's failure to metabolize. The deficiency stems from biallelic variants of the AMACR gene, which is responsible for encoding the fatty acyl methyl group racemases, that transform (R)-pristanic acid and C27-bile acid intermediates into their (S)- counterparts. These (S)- versions are accessible to further degradation in β-oxidation of peroxisomes. The absence of functional AMACR leads to the relentless accumulation of toxic metabolites, resulting in an extensive spectrum of manifestations including neurological deficits, hepatic pathology, and retinal dystrophy.

Schematic representation of the functions of AMACR.

Fig.1 Schematic representation of the functions of alpha-methylacyl-CoA racemase (AMACR). (Klouwer F. C., et al., 2024)

Diagnostics Development for AMACR

Biochemical Analysis

A biochemical assessment stands as the cornerstone of the diagnostics for an AMACR deficiency. Furthermore, the diagnostic criteria include increased concentrations of Pristanic acid, DHCA ,and THCA found in the plasma. The metabolites quantification using UPLC-MS/MS can be performed readily which makes it easy to confirm the condition. Moreover, the analysis of urine can also reveal C27 bile acid intermediate forms reinforcing the diagnosis.

Genetic Testing

For a conclusive diagnosis of Alpha-Methylacyl-CoA Racemase Deficiency (AMACR) deficiency, genetic testing is a prerequisite. Biallelic AMACR gene variants are detected via NGS panels focused on peroxisomal disorders. Such an approach has the capability to identify pathogenic variants, thus confirming the disorder at a molecular level. Genetic testing is vital in the context of family screening and carrier detection.

Therapeutics of AMACR

Therapeutics	Target	Description	Stage
Dietary Restriction of Phytanic Acid	Phytanic Acid Metabolism	Restricting dietary intake of phytanic acid helps reduce the accumulation of pristanic acid, a toxic metabolite in AMACR deficiency. This approach is currently used to manage symptoms and slow disease progression.	Approved
Antiepileptic Drugs	Seizure Management	Used to manage seizures in patients with AMACR deficiency. These drugs help control seizure activity and improve quality of life.	Approved
Cholic Acid Supplementation	Bile Acid Synthesis	Cholic acid supplementation aims to suppress bile acid synthesis, thereby reducing the accumulation of toxic C27-bile acid intermediates. While its efficacy in AMACR deficiency has not been systematically studied, it has shown promise in other peroxisomal disorders.	Preclinical
Gene Therapy	AMACR Gene Expression	Gene therapy approaches aim to restore functional AMACR expression in affected tissues. This involves using viral vectors to deliver a functional copy of the AMACR gene, potentially correcting the underlying genetic defect.	Preclinical

Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.

Our Services

Protheragen provides complete diagnostics and therapeutics development services for Alpha-Methylacyl-CoA Racemase Deficiency (AMACR). We provide multi-faceted, diagnostic frameworks such as biochemical assessments, genetic evaluations, and sophisticated imaging to facilitate prompt and precise diagnostic outcomes. Furthermore, we customize therapy development through diverse approaches such as small-molecule agents as well as novel gene therapy approaches.

Diagnostics Development

Therapeutic Development

Preclinical Research

Disease Models

Induced Pluripotent Stem Cells (iPSCs)
AMACR Gene Knockout Mouse Models
AMACR Gene Knockout Zebrafish Models

Protheragen's diagnostics and therapeutics development services for AMACR deficiency are characterized by their comprehensive and integrated approach. If you are interested in our services, please feel free to contact us.

References

Klouwer, Femke CC, et al. "Redefining the phenotype of alpha-methylacyl-CoA racemase (AMACR) deficiency." Orphanet Journal of Rare Diseases 19.1 (2024): 350.
Selamioğlu, Arzu, et al. "Variable clinical phenotypes of alpha‐methylacyl‐CoA racemase deficiency: Report of four cases and review of the literature." JIMD reports 65.5 (2024): 305-312.