The diagnostic challenge in very-long chain acyl-CoA dehydrogenase deficiency (VLCADD)

In this study, we show the outcome of enzyme testing in lymphocytes a s a confirmatory tool in newborns identified by screening, and the correlation with molecular sequencing of theACADVL gene. From April 2013 to March 2017, in 403 individuals with characteristic acylcarnitine profiles indicative of VLCADD, palmitoyl-CoA oxidation was measured followed by molecular genetic analysis in most of the patients with residual activity (RA)<50%. In almost 50% of the samples (209/403) the RA was>50%, one-third of the individuals (125/403) displayed a RA of 30 –50% and 69/403 individuals showed a residual activity of 0–30%. Sequencing of theACADVL gene revealed that all individuals with activities below 24% were true VLCADD patients, individuals with residual activities between 24 and 27% carried either one or two mutations. Twenty new mutations could be identified and functionally classified based on their effect on enzyme function. Finally, we observed an up-regulation of MCAD-activity in many patients. However, this did not correlate with the degree of VLCAD RA. Although the likely clinical phenotype cannot be fully foreseen by genetic and functional tests as it depends on many factors, our data demonstrate the strength of this functional enzyme test in lymphocytes as a quick and reliable method for confirmation diagnostics of VLCADD.
Source: Journal of Inherited Metabolic Disease - Category: Internal Medicine Source Type: research