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Long-Chain Fatty Acid Oxidation Disorder Genes: A Comprehensive Genetic Database of LC-FAOD Variants, Genotypes, and
Heather Richbourg1, Vanessa Rangel Miller1, Omid Khazaie Japalaghi1
1Ultragenyx Pharmaceutical Inc., Novato, California, USA.
Human Mutation
|July 9, 2026
Summary
A new database centralizes genetic variants for long-chain fatty acid oxidation disorders (LC-FAODs), aiding diagnosis and research. It compiles variant data, clinical details, and outcomes for these rare metabolic diseases.
Area of Science:
- Biochemistry and Genetics
- Metabolic Disorders
- Bioinformatics
Background:
- Long-chain fatty acid oxidation disorders (LC-FAODs) are rare genetic conditions impairing fatty acid metabolism, leading to severe health issues like cardiomyopathy and liver failure.
- Diagnosing LC-FAODs is challenging due to their rarity, genetic diversity, and numerous variants of uncertain significance.
- A comprehensive resource is needed to consolidate and disseminate information on LC-FAOD-associated genetic variants.
Purpose of the Study:
- To establish a locus-specific database for variants in the six key genes implicated in LC-FAODs.
- To collect, curate, and present comprehensive data on genetic variants, genotypes, and phenotypes related to LC-FAODs.
- To facilitate research and improve diagnostic accuracy for LC-FAODs.
Main Methods:
- Conducted a systematic literature review to identify disease-associated variants.
- Integrated data from a sponsored gene panel program, including clinical and biochemical information.
- Stored curated variant data, including genotypes and phenotypes, in a robust database system (MongoDB and MySQL).
Main Results:
- The database contains 6947 variants from 4188 individuals across six LC-FAOD genes (ACADVL, CPT1A, CPT2, HADHA, HADHB, SLC25A20).
- ACADVL variants are most frequent (40%), followed by HADHA (25%) and CPT2 (21%).
- Detailed clinical data, including phenotypes (1496 individuals), newborn screening results (2589), and enzyme activity assays (499), are available. Severe outcomes were reported for 219 individuals, with HADHA p.Glu510Gln homozygosity being the most common genotype.
Conclusions:
- The LC-FAOD gene database serves as a vital, comprehensive resource for variants, genotypes, and phenotypes.
- This curated database aids researchers and clinicians in understanding and diagnosing LC-FAODs.
- The public accessibility of the database promotes collaboration and advances the study of these critical metabolic disorders.
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