Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Research Unit for Molecular Medicine, |
RCV001290987 | SCV001432710 | likely pathogenic | Deficiency of butyryl-CoA dehydrogenase | 2019-09-12 | criteria provided, single submitter | research | ECHDC1 encodes a 'metabolite repair enzyme' detoxifying ethylmalonic acid (EMA), which is the biochemical hallmark of short-chain acyl-CoA dehydrogenase deficiency (OMIM:201470), caused by biallelic ACADS variants. We provide functional evidence that ECHDC1 c.498-36_498-33del4bp is a loss-of function (LOF) variant. The variant was identified in the heterozygous state together with a heterozygous ACADS NM_000017.2: c.625G>A susceptibility variant. We provide functional evidence that ECHDC1 haploinsufficiency in combination with ACADS c.625G>A susceptibility variants has a synergistic effect on cellular EMA levels. In a cohort of 82 genetically unsolved EMA patients, we found three unrelated cases with heterozygous LOF ECHDC1 variants combined with ACADS c.625G>A suceptibility variants. |