Genomic newborn screening: ICoNS
Gene: ACADVL
Well established gene-disease association.
VLCAD deficiency can be classified clinically into 3 forms: a severe early-onset form with high incidence of cardiomyopathy and high mortality; an intermediate form with childhood onset, usually with hypoketotic hypoglycemia and more favorable outcome; and an adult-onset, myopathic form with isolated skeletal muscle involvement, rhabdomyolysis, and myoglobinuria after exercise or fasting.
- Severe disease is associated with no residual enzyme activity, often resulting from null variants. Approximately 81% of pathogenic truncating variants in ACADVL are associated with the severe early-onset form [Andresen et al 1999].
- A specific homozygous missense pathogenic variant (c.709T>C;p.Cys237Arg) leading to low long-chain fatty acid oxidation flux may also be associated with cardiac disease [Diekman et al 2015].
- Milder childhood and adult forms are often associated with residual enzyme activity. The common p.Val283Ala variant, in both homozygous and compound heterozygous genotypes, is typically associated with the non-cardiac phenotypes [Spiekerkoetter et al 2009, Diekman et al 2015, Miller et al 2015].
Treatment: avoid fasting, carnitine, restrict LCFA, bezafibrate, triheptanoin
On BabyScreen+, BabySeq, BeginNGS, Guardian, Generation and EarlyCheck
Sources: Expert listCreated: 20 May 2025, 4:43 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
VLCAD deficiency MIM#201475
Publications
gene: ACADVL was added gene: ACADVL was added to Genomic newborn screening: ICoNS. Sources: Expert list Mode of inheritance for gene: ACADVL was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ACADVL were set to PMID: 20301763; 32885845; 31372341 Phenotypes for gene: ACADVL were set to VLCAD deficiency MIM#201475 Review for gene: ACADVL was set to GREEN