Researchers from Italy identified a novel pathogenic missense variant in the ACADVL gene, which is associated with very-long-chain acyl-coenzyme A (CoA) dehydrogenase (VLCAD) deficiency, a type of long-chain fatty acid oxidation disorder (LCFAOD). They said this “expands the allelic heterogeneity of the disease.”

“Since dietary treatment is the only therapy available for treating VLCAD deficiency and it is more useful the earlier it is started, prompt diagnosis is essential in order to minimize muscle damage and slow the disease progression,” they added. 

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The study is published in the journal Brain Sciences.

The novel variant was identified in a 17-year-old male who had exercise-induced muscle pain and fatigue since childhood. He also had episodes of exercise-related severe hyperCKemia and myoglobinuria. 

He underwent an electromyography, which was normal. A muscle biopsy was also taken and revealed “moth-eaten” fibers and a mild increase in lipid storage. 

The researchers also conducted a next-generation sequencing and saw that the patient had the already known heterozygote c.1769G>A variant. However, he also had a heterozygote c.523G>C change in the ACADVL gene, which has not been reported previously. 

When they analyzed the patient’s plasma acylcarnitine profiles, the researchers found he had high levels of long-chain acylcarnitine species, especially C14:1. 

He was finally diagnosed with VLCAD deficiency based on the results of the biochemical, histopathological, clinical, and genetic tests.

VLCAD deficiency is 1 of 6 types of LCFAOD. The faulty gene normally encodes an enzyme that is essential for the beta oxidation of fatty acids inside the mitochondria. Defects in this enzyme due to mutations in the ACADVL gene lead to energy deficiency and fatty acid accumulation that is toxic to cells. 


Labella B, Lanzi G, Cotti Piccinelli S, et al. Juvenile-onset recurrent rhabdomyolysis due to compound heterozygote variants in the ACADVL gene. Brain Sci. Published online August 8, 2023. doi:10.3390/brainsci13081178