This report describes mitochondrial trifunctional protein deficiency, HADHA-related. Mitochondrial trifunctional protein deficiency (MIM:609015) can be caused by mutation in either HADHA or HADHB; in both cases, it exhibits autosomal recessive inheritance. The HADHB gene encodes the alpha subunit of the mitochondrial trifunctional protein. There is one fly ortholog, Mtpα, for which RNAi targeting constructs, alleles caused by insertional mutagenesis, and an amorphic allele created by targeted recombination have been generated. See also the human disease model report for 'mitochondrial trifunctional protein deficiency, HADHB-related' (FBhh0000338). HADHA is also associated with the human disease long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (MIM:609016, FBhh0000332).
A UAS construct of the wild-type human Hsap\HADHA gene has been introduced into flies, but has not been used to investigate disease.
Animals homozygous for an amorphic allele of Dmel\Mtpα have a shorter lifespan and locomotor defects; females exhibit reduced fertility. In addition, they are hypersensitive to fasting, have lower survival and starvation conditions, and retain lipid droplets in their fat body cells in non-fasting conditions. Physical interactions have been described for Mtpα; see below and in the Mtpα gene report.
[updated Jul. 2017 by FlyBase; FBrf0222196]
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]
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).
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]).
See also isolated LCHAD deficiency (MIM:609016), which is caused by mutation in the HADHA gene. [From MIM:609015, 2016.06.16]
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]
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).
See also isolated LCHAD deficiency (MIM:609016), which is caused by mutation in the HADHA gene. [From MIM:609015, 2016.06.16]
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 gene encodes the alpha subunits of the mitochondrial trifunctional protein. 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. (Kamijo et al., 1994, pubmed:8135828). [From MIM:600890 and MIM:143450, 2016.06.16]
One to one: 1 human to 1 Drosophila.
Ortholog of human HADHA (1 Drosophila to 1 human). Dmel\Mtpα shares 55% identity and 72% similarity with human HADHA.
