Newborns with C8-acylcarnitine level over the 90th centile have an increased frequency of the common MCAD 985A>G mutation

(M)edium chain acyl-coenzyme A dehydrogenase (MCAD) deficiency is the most commonly inherited defect of fatty acid oxidation. This autosomal recessive disorder is characterized by the tendency to become profoundly hypoglycaemic under fasting stress conditions, leading to lethargy, coma, brain injury and/or death. The most common mutation resulting in MCAD deficiency ascertained through individuals of northern European descent presenting with clinical symptoms is a single base-pair change (985A > G) that accounts for up to 90% of these abnormal alleles. In the general Nova Scotia population, which comprises largely individuals of northern European descent, this mutation is present at a frequency of 1 in 68. A recently implemented newborn screening programme for MCAD deficiency uses tandem mass spectrometry (MS/MS) to analyse blood spots from newborns for C-8-acylcarnitine. After reviewing initial data from this newborn screening programme, we hypothesized that there was an unexpectedly high frequency of individuals with an MCAD 985A > G mutation and C-8-acylcarnitine levels at the upper end of the normal range. A sample representing the upper 90th centile was screened for the presence of the 985A > G mutation and 61 heterozygotes were identified, establishing a high frequency (1/10) of this 985A > G mutation in this selected population. We have demonstrated a relationship between heterozygosity for 985A > G and C-8-acylcarnitine levels. These results contribute to the interpretation of C-8-acylcarnitine levels and the establishment of a more clinically relevant screening cut-off point.