The natural history of medium-chain acyl CoA dehydrogenase deficiency in the Netherlands: Clinical presentation and outcome

Prolonged QTc Interval in Association With Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency

“…However, in a study from The Netherlands, 15 of 120 individuals were diagnosed with MCAD deficiency on the basis of clinical presentation before the availability of newborn screen results. 1 The importance of prompt recognition of MCAD deficiency in the symptomatic neonate is underscored by a 5% risk of mortality. 2 Therefore, a high index of suspicion for inborn errors of metabolism in critically ill neonates should be maintained, because results from the blood spot newborn screen are often not available until after 72 hours of life.…”

“…Patients who survive acute decompensation remain at risk of subsequent psychomotor developmental delays and behavioral problems. 1 When MCAD deficiency is suspected as a result of clinical presentation or from an abnormal newborn screen, confirmatory testing including plasma acylcarnitines, urine acylglycines, and urine organic acids should be assessed. Diagnosis can also be confirmed via mutation analysis of the ACADM gene.…”

Medium-Chain Acyl-CoA Dehydrogenase Deficiency: Evaluation of Genotype-Phenotype Correlation in Patients Detected by Newborn Screening

“…Thus, it does not seem safe to predict a completely asymptomatic clinical phenotype from the milder biochemical phenotype. Neonatal hypoglycaemia or death has been reported in patients with MCADD diagnosed symptomatically (Wilcken et al 1994;Derks et al 2006;Wilcken et al 2007). However, it could be discussed that neonatal hypoglycaemia in our patients might have been unrelated to MCADD.…”

“…Outcome is predominantly excellent following presymptomatic diagnosis, if prolonged fasting is avoided and adequate emergency management is performed during episodes of metabolic stress (Wilcken et al 2007;Lindner et al 2011). In cohorts diagnosed symptomatically, about 20% of patients died from their first metabolic decompensation, 20% showed severe neurological sequelae (Derks et al 2006). In these cohorts, the c.985A>G mutation in the ACADM gene accounted for about 90% of disease-causing alleles (Gregersen et al 1991;Yokota et al 1991;Derks et al 2006).…”

“…In cohorts diagnosed symptomatically, about 20% of patients died from their first metabolic decompensation, 20% showed severe neurological sequelae (Derks et al 2006). In these cohorts, the c.985A>G mutation in the ACADM gene accounted for about 90% of disease-causing alleles (Gregersen et al 1991;Yokota et al 1991;Derks et al 2006). In addition to this most common mutation in Europe, in screening cohorts other mutations, especially c.199T>C, are frequently found (Ziadeh et al 1995;Andresen et al 2001;Maier et al 2005;Waddell et al 2006;Hsu et al 2008).…”