Alternative titles; symbols
SNOMEDCT: 237955004;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 6q25.3 | ?ACAT2 deficiency | 614055 | Isolated cases | 1 | ACAT2 | 100678 |
De Groot et al. (1977) reported a child, born of unrelated parents, who had normal development until about 3 to 4 months of age, when she showed a slowing in motor development and even some loss in acquired motor abilities. At age 14 months, she had poor head control and was unable to sit or roll over. She had ataxic and choreic movements, with involuntary vertical ocular movements. She also had severely impaired cognitive development at age 16 months. Laboratory studies showed increased serum lactate and pyruvate, and high levels of ketones on a ketogenic diet. This suggested impaired utilization of ketones. Liver biopsy showed low levels of cytosolic acetoacetyl-CoA thiolase (ACAT2; 100678), and the enzyme showed increased sensitivity to inhibition by CoA with decreased affinity for acetoacetyl-CoA compared to control. Liver biopsy also showed increased deposition of fat lipid droplets and glycogen accumulation. De Groot et al. (1977) postulated that the severe neurologic phenotype in this patient resulted from a disruption in lipid processing in the brain.
Bennett et al. (1984) reported a boy, born of unrelated parents, who presented at age 7 months with hypotonia, pyrexia, and screaming, and was found to have severe developmental delay with abnormal EEG. Laboratory studies showed increased urinary ketones. Cultured fibroblasts showed a 50% reduction in activity of cytosolic acetoacetyl-CoA thiolase. A low-fat diet was instituted, which resulted in reduction of ketosis. After the low-fat diet was instituted, he developed severe gastrointestinal problems consistent with colitis cystica superficialis, which responded to steroid treatment.
Bennett, M. J., Hosking, G. P., Smith, M. F., Gray, R. G. F., Middleton, B. Biochemical investigations on a patient with a defect in cytosolic acetoacetyl-CoA thiolase, associated with mental retardation. J. Inherit. Metab. Dis. 7: 125-128, 1984. [PubMed: 6150136] [Full Text: https://doi.org/10.1007/BF01801770]
de Groot, C. J., Luit-de Haan, G., Hulstaert, C. E., Hoomes, F. A. A patient with severe neurologic symptoms and acetoacetyl-CoA thiolase deficiency. Pediat. Res. 11: 1112-1116, 1977. [PubMed: 20597]