Medium-chain acyl-CoA dehydrogenase deficiency: Genotype–biochemical phenotype correlations

Relevance of Expanded Neonatal Screening of Medium-Chain Acyl Co-A Dehydrogenase Deficiency: Outcome of a Decade in Galicia (Spain)

“…Similar to other studies, the prevalent mutation in our population is c.985A>G (p.K329E), which was found in 75% of the alleles with MCADD, but was not as high as previously anticipated (Yokota et al 1991;Giroux et al 2007;Waddell et al 2006;Blois et al 2005), although it is rather high if we consider other neonatal screening studies (Andresen et al 2001;Maier et al 2005;Nichols et al 2008;Smith et al 2010) as in the screened individuals it is usual to find milder mutations, while the common mutation c.985A> G is most frequently found in the clinically presenting patients.…”

“…It seems that there is no clear relationship between genotype and phenotype (Andresen et al 1997;Lehotay et al 2004;Waddell et al 2006;Hsu et al 2008), but patients homozygous for the common mutation have higher levels of C8 (Andresen et al 2001;Waddell et al 2006;Smith et al 2010), and it is associated with a greater predisposition to suffer decompensation in situations of metabolic stress (Arnold et al 2010). Thus, compound heterozygous for the prevalent c.985A>G mutation and a milder mutation in the other allele may have a risk reduction due to their greater residual enzyme activity (Lehotay et al 2004).…”

“…To date, 81 ACADM mutations have been described in the Human Genome Mutation database http://www.hgmd.cf.ac.uk, but a clear genotypephenotype correlation has not been established, and there is a wide phenotypic variability even within the same family (Yokota et al 1991;Andresen et al 1997;Lehotay et al 2004;Waddell et al 2006;Hsu et al 2008).…”

“…Clinical symptoms are diverse ranging from asymptomatic to hypoketotic hypoglycemic episodes and even sudden death in some patients (Andresen et al 1993(Andresen et al , 2001Waddell et al 2006). Symptoms could occur at any age and are typically precipitated by stress in situations of high energy demand such as a prolonged period of fasting or an intercurrent illness, particularly between 3 and 24 months of age.…”

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

“…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). There is ongoing discussion, whether patients with this potentially mild mutation would ever show any clinical phenotype (Andresen et al 2001) or might not require treatment at all (Sturm et al 2012).…”