Likely inborn error of metabolism - targeted testing not possible
Gene: ACACA
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
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: LiteratureCreated: 4 Dec 2023, 2:03 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Acetyl-CoA carboxylase deficiency
Publications
Publications for gene: ACACA were updated from 6114432; 16103361; 34552920; 36709796 to 6114432; 34552920; 36709796
Publications for gene: ACACA were set to 6114432; 34552920; 36709796
Tag Q4_23_promote_green tag was added to gene: ACACA. Tag Q4_23_NHS_review tag was added to gene: ACACA.
Publications for gene: ACACA were set to 34552920; 36709796
Publications for gene: ACACA were set to 34552920; 36709796
Publications for gene: ACACA were set to 34552920
Phenotypes for gene: ACACA were changed from Acetyl-CoA carboxylase deficiency to Acetyl-CoA carboxylase deficiency, OMIM: 613933
Gene: acaca has been classified as Amber List (Moderate Evidence).
gene: ACACA was added gene: ACACA was added to Likely inborn error of metabolism - targeted testing not possible. Sources: Literature Mode of inheritance for gene: ACACA was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ACACA were set to 34552920 Phenotypes for gene: ACACA were set to Acetyl-CoA carboxylase deficiency Review for gene: ACACA was set to AMBER