Researchers identified a novel mutation in the ACADVL gene causing very long-chain acyl-coenzyme-A dehydrogenase (VLCAD) deficiency, a type of long-chain fatty acid oxidation disorder (LCFAOD), in a baby from Sri Lanka. They presented their finding in a case report published in the Journal of Medical Case Reports.
The baby developed bronchopneumonia with heart failure secondary to cardiomyopathy, recurrent convulsions, and hypoglycemic events. She died at 4 months of age.
“This case demonstrates the importance of early diagnosis and management of [VLCAD deficiency] in improving the outcome of the patients,” Visvalingam Arunath and the coauthors of the study wrote. They suggested that the implementation of newborn screening in Sri Lanka will be beneficial in reducing the morbidity and mortality of treatable disorders such as LCFAODs.
Read more about LCFAOD etiology
The ACADVL gene encodes the VLCAD enzyme that is part of the long-chain beta-oxidation spiral, which processes long-chain fatty acids inside the mitochondria. Mutations in the ACADVL gene prevent the VLCAD enzyme from functioning properly, leading to long-chain fatty acids not being broken down and resulting in low energy and cell damage.
Here, the researchers identified a homozygous frameshift variant, NM_001270447.1, c.711_712del p.(Phe237Leufs*38), in the ACADVL gene of the patient.
“The variant is novel and is absent in gnomAD (accession date 14 February 2020),” the researchers wrote. “It is classified as likely pathogenic based on the American College of Medical Genetics and Genomic guidelines.”
The baby was born by spontaneous vaginal delivery at term weighing 2910 g (approximately 6.4 lbs). At birth, she had hypotonia and an enlarged liver. She developed grunting, poor feeding, and recurrent episodes of symptomatic hypoglycemia and convulsions. Blood tests revealed that she had metabolic acidosis, elevated transaminases, and high levels of serum creatine phosphokinase. She had an echocardiogram at 4 months of age that showed bilateral ventricular hypertrophy. She also had high concentrations of tetradecanoylcarnitine (C14), C14:1, and C14:1 to C16 ratio.
Arunath V, Liyanarachchi MS, Gajealan S, Jasinge E, Weerasekara K, Moheb LA. A novel mutation in ACADVL causing very long-chain acyl-coenzyme-A dehydrogenase deficiency in a South Asian pediatric patient: a case report and review of the literature. J Med Case Rep. 2021;15(1):441. doi:10.1186/s13256-021-03013-y