Likely inborn error of metabolism

Gene: ACACA

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 4 May 2024, 3:17 p.m. | Last Modified: 4 May 2024, 3:17 p.m.

Panel Version: 5.3

ACACA variants have been associated with Acetyl-CoA carboxylase deficiency (OMIM: 613933), but not associated with phenotype in Gen2Phen. At least three reports of Acetyl-CoA carboxylase deficiency have been published (PMID: 6114432;34552920;36709796). However, genetic analysis was only possible in two of these cases; the resulting three ACACA variants were reported in two unrelated cases, demonstrating a biallelic mode of inheritance, with heterozygous ACACA variants in the unaffected parents (PMID: 34552920;36709796). In vitro functional studies, suggest that the level of ACACA expression is not severely affected, but revealed a disruption of lipid homeostasis in patient-derived lymphocytes, further inducing the deficit of cell motility capacity and that the deficiency could be partly attenuated by palmitate (PMID: 34552920). Furthermore, embryonic lethality was seen in mice who were homozygous for a knock-out ACACA variant, while those who were heterozygous for the variant presented with no obvious phenotypes (PMID: 16103361).

Created: 2 Jan 2024, 3:16 p.m. | Last Modified: 2 Jan 2024, 3:16 p.m.

Panel Version: 4.81

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

I don't know

PMID: 34552920 (2021) reported a baby who presented in her first two years of life with global developmental delay, microcephaly, hypotonia, and dysmorphic facial features. Two VUS's in ACACA were identified, and a decreased level of ACC1 and ACC1 enzyme activity was detected in patient-derived lymphocytes. In vitro studies revealed a disruption of lipid homeostasis in patient-derived lymphocytes, further inducing the deficit of cell motility capacity and that the deficiency could be partly attenuated by palmitate.
Sources: Literature

Created: 4 Dec 2023, 2:03 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Acetyl-CoA carboxylase deficiency

Publications

• 34552920