Data from the Swedish newborn screening (NBS) program suggested that patients with very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency who were diagnosed through the program had less severe phenotypes than those clinically diagnosed. VLCAD deficiency is a type of long chain fatty acid oxidation disorder (LCFAOD).
“There is a clear difference between the clinically diagnosed patients who had severe symptoms early in life and the NBS group, although heterogenous, which displayed milder courses of disease,” the authors said.
In addition, the authors found a positive correlation between the Collaborative Laboratory Integrated Reports (CLIR) score and the clinical severity score (CSS). CLIR is a web-based interactive database that includes NBS results from numerous screening sites and is used to improve NBS performance.
The CSS included the evaluation of 15 criteria, each scored with 1 point if present (CSS range, 0-15). The researchers also found negative correlations between the palmitoyl-CoA oxidation rate and both the CLIR score and CSS.
“The screening CLIR score in combination with the residual enzyme activity, and genetic analysis may be useful in predicting disease severity and the need for dietary treatment already in the neonatal period,” the authors wrote.
Read more about LCFAOD treatment
In this study, most (n=19) patients were maintained on a fat-restricted diet. Also, 18 patients were prescribed supplementation medium-chain triglycerides.
Genetic studies identified the c.848T>C variant of the ACADVL gene as the most prevalent in this study cohort (24/44 alleles). In addition, the authors identified novel mutations in 5 patients, all of which were predicted to be pathogenic by in silico analysis.
The study enrolled 20 patients diagnosed via NBS since 2010 and 2 patients diagnosed clinically before the implementation of the screening program. Only 4 patients presented with symptoms neonatally.
Olsson D, Barbaro M, Haglind C, et al. Very long‐chain acyl‐CoA dehydrogenase deficiency in a Swedish cohort: clinical symptoms, newborn screening, enzyme activity, and genetics. JIMD Rep. Published online January 9, 2022. doi:10.1002/jmd2.12268