Table 1.
Genes involved in CoA/Acetyl-CoA biosynthesis or transport and associated neurological disorders.
| Gene (OMIM *) |
Protein Function | Disorder (OMIM °) |
Inheritance | Clinical Features | Molecules Investigated for Therapeutic Potential |
|---|---|---|---|---|---|
| PANK2 (606157) |
PANK2 catalyzes the phosphorylation of pantothenate to 4-phosphopantothenate, first step of CoA biosynthesis. |
Pantothenate kinase-associated neurodegeneration -PKAN (234200) |
AR | Early (childhood) or late (early adulthood) onset. Dystonia, spasticity, parkinsonism, retinal degeneration, cognitive decline, neuropsychiatric disturbances. | Pantothenate; Pantethine; Fosmetpantotenate; 4′-Phosphopantetheine and Acetyl-4′-Phosphopantetheine; Coenzyme A; Pantazines; Artesunate; Deferiprone |
| COASY (609855) |
COASY catalyzes the two final steps of CoA biosynthesis. | COASY Protein-Associated Neurodegeneration–CoPAN (615643) |
AR | Early onset gait impairment and learning difficulties, with dystonia, and spasticity. | Coenzyme A |
| SLC25A42 (610823) |
Mitochondrial CoA transporter | Recurrent metabolic crises with variable encephalomyopathic features and neurologic regression -MECREN (618416) |
AR | Usually childhood onset with episodic lactic acidosis. Possible developmental regression of motor and cognitive skills. | - |
| SLC33A1 (603690) |
Endoplasmic Reticulum acetyl-CoA transporter | Congenital cataracts, hearing loss, and neurodegeneration -CCHLNDH-uppke and Brendel syndrome (614482) |
AR | Severe psychomotor retardation, congenital cataracts and hearing loss. More variable neurologic features. Low copper and ceruloplasmin serum levels. | - |
| Spastic paraplegia 42 (612539) |
AD - rs121909484 (p.S113R) in the Chinese population. |
Spastic gait, increased lower limb tone, hyperreflexia, and weakness and atrophy of the lower limb muscles. | - | ||
| Autism-spectrum disorder with intellectual disability | AD (gene duplication) |
- | - |
OMIM: online mendelian inheritance in man, https://www.omim.org (accessed on 5 July 2021); * Gene MIM; ° Phenotype MIM; AR autosomal recessive; AD autosomal dominant.