This report describes mitochondrial trifunctional protein deficiency. The human genes implicated in this disease are HADHA and HADHB, which encode the alpha and beta subunits of the mitochondrial trifunctional protein. HADHA is also associated with the human disease long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (MIM:609016, FBhh0000332). There is one fly ortholog for each of these genes, MtpĪ± and MtpĪ², respectively. See the human disease model reports 'mitochondrial trifunctional protein deficiency 1' (FBhh0000337) and 'mitochondrial trifunctional protein deficiency 2' (FBhh0000338) for information relevant to the fly disease models.
[updated May 2025 by FlyBase; FBrf0222196]
Some patients with MTP deficiency show a protracted progressive course associated with myopathy, recurrent rhabdomyolysis, and sensorimotor axonal neuropathy. These patients tend to survive into adolescence and adulthood (den Boer et al., 2003, pubmed:12838198]).
Mitochondrial trifunctional protein deficiency is a rare condition that prevents the body from converting certain fats to energy, particularly when fasting.
Signs and symptoms of mitochondrial trifunctional protein deficiency may begin during infancy or later in life. Features that occur during infancy include feeding difficulties,lethargy, hypoglycemia, hypotonia, and liver problems. Infants with this disorder are also at high risk for serious heart problems, breathing difficulties, coma, and sudden death. Signs and symptoms of mitochondrial trifunctional protein deficiency that may begin after infancy include hypotonia, muscle pain, a breakdown of muscle tissue, and peripheral neuropathy. Problems related to mitochondrial trifunctional protein deficiency can be triggered by periods of fasting or by illnesses such as viral infections. [From Genetics Home Reference, mitochondrial trifunctional protein deficiency, 2016.06.16]
See also isolated LCHAD deficiency (MIM:609016), which is caused by mutation in the HADHA gene. [From MIM:609015, 2016.06.16]
The mitochondrial trifunctional protein, composed of 4 alpha and 4 beta subunits, catalyzes 3 steps in mitochondrial beta-oxidation of fatty acids: long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD), long-chain enoyl-CoA hydratase, and long-chain thiolase activities. Trifunctional protein deficiency is characterized by decreased activity of all 3 enzymes. Clinically, classic trifunctional protein deficiency can be classified into 3 main clinical phenotypes: neonatal onset of a severe, lethal condition resulting in sudden unexplained infant death (SIDS; MIM:272120), infantile onset of a hepatic Reye-like syndrome, and late-adolescent onset of primarily a skeletal myopathy (Spiekerkoetter et al., 2003, pubmed:12754706).
Mitochondrial trifunctional protein deficiency (MTPD) is caused by homozygous or compound heterozygous mutation in the genes encoding either the alpha (HADHA) or beta (HADHB) subunits of the mitochondrial trifunctional protein. [From MIM:609016, 2015.06.16]
The HADHA and HADHB genes encode the alpha and beta subunits of the mitochondrial trifunctional protein, respectively. The heterocomplex contains 4 alpha and 4 beta subunits and catalyzes 3 steps in mitochondrial beta-oxidation of fatty acids, including the long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) step. The alpha subunit harbors the 3-hydroxyacyl-CoA dehydrogenase and enoyl-CoA hydratase activities, while the beta subunit harbors the 3-ketoacyl-CoA thiolase activity. (Kamijo et al., 1994, pubmed:8135828). [From MIM:600890 and MIM:143450, 2016.06.16]
