Mitochondrial trifunctional protein (TFP) deficiency is a rare autosomal recessive disorder that is caused by mutations in HADHA and HADHB. TFP is a multienzyme complex of the fatty acid beta-oxidation cycle. Human TFP is an octamer composed of four alpha-subunits harboring long-chain enoyl-CoA hydratase and long-chain L-3-hydroxyacyl-CoA dehydrogenase (LCHAD) and four beta-subunits encoding long-chain 3-ketoacyl-CoA thiolase (LCKAT). This disease includes a lethal neonatal phenotype with cardiomyopathy and Reye-like syndrome, an infantile hepatic phenotype with recurrent hypoketotic hypoglycemia, and a childhood or adolescent-onset neuromyopathic phenotype with peripheral neuropathy and recurrent rhabdomyolysis.
Human diseases in ICD-11 classification [BR:br08403]
05 Endocrine, nutritional or metabolic diseases
Metabolic disorders
Inborn errors of metabolism
5C52 Inborn errors of lipid metabolism
H01352 Mitochondrial trifunctional protein deficiency
Pathway-based classification of diseases [BR:br08402]
Lipid/glycolipid metabolism
nt06020 beta-Oxidation in mitochondria
H01352 Mitochondrial trifunctional protein deficiency
Spiekerkoetter U, Khuchua Z, Yue Z, Bennett MJ, Strauss AW
Title
General mitochondrial trifunctional protein (TFP) deficiency as a result of either alpha- or beta-subunit mutations exhibits similar phenotypes because mutations in either subunit alter TFP complex expression and subunit turnover.
Accumulation of 3-hydroxy-fatty acids in the culture medium of long-chain L-3-hydroxyacyl CoA dehydrogenase (LCHAD) and mitochondrial trifunctional protein-deficient skin fibroblasts: implications for medium chain triglyceride dietary treatment of LCHAD deficiency.
Molecular characterization of mitochondrial trifunctional protein deficiency: formation of the enzyme complex is important for stabilization of both alpha- and beta-subunits.