Children with MCAD deficiency had normal growth. p.Lys329Glu homozygotes had higher NBS C8-carnitine (23.4 ± 19.6 vs. 6.6 ± 3.0 μmol/L) and lifetime plasma C8-carnitine levels (6.2 ± 5 vs. 3.6 ± 1.9 μmol/L) compared to patients with at least one other pathogenic variant (p < .001 for both) and higher transaminases compared to compound heterozygotes (ALT 41.9 ± 6.2 vs. 31.5 ± 3.7 U/L, AST 63.9 ± 5.8 vs. 45.7 ± 1.8 U/L, p < .05 for both).
The newborn screen was suggestive for MCAD deficiency, a diagnosis that was confirmed on genetic analysis that showed homozygosity for the disease-associated missense A985G mutation in the ACADM gene.
The newborn screen was suggestive for MCAD deficiency, a diagnosis that was confirmed on genetic analysis that showed homozygosity for the disease-associated missense A985G mutation in the ACADM gene.
Pathogenic variants for Mendelian and complex traits in exomes of 6,517 European and African Americans: implications for the return of incidental results.
An empirical estimate of carrier frequencies for 400+ causal Mendelian variants: results from an ethnically diverse clinical sample of 23,453 individuals.
Therefore, this variant along with the c.985A>G allele could constitute a panel for both prenatal and neonatal MCADD screening in the Greek population.
We suggest that in MCADD (1) a newborn screening C8 level of 6micromol/L or greater represents particular risk of sudden death; (2) that MCAD genotypes other than homozygosity for the c.985A>G mutation are also associated with sudden death; (3) that vomiting is a frequent symptom preceding sudden death; and (4) social support and medical follow-up of these families are crucial in reducing the occurrence of sudden death.
Associated with heterozygosity for c.985A>G mutation, this mutation is responsible for a mild MCADD phenotype along with a clinical story corroborating the emerging literature view that patients with genotypes representing mild MCADD (high residual enzyme activity and low urinary levels of glycine conjugates), similar to some of the mild MCADDs detected by MS/MS newborn screening, may be at risk for disease presentation.