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General Information
Name
mitochondrial trifunctional protein deficiency
FlyBase ID
FBhh0000333
Disease Ontology Term
Parent Disease
Overview

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 (OMIM:609016, FBhh0000332). There is one fly ortholog for each of these genes, MtpĪ± and Thiolase, respectively. See the human disease model reports 'mitochondrial trifunctional protein deficiency, HADHA-related' (FBhh0000337) and 'mitochondrial trifunctional protein deficiency, HADHB-related' (FBhh0000338) for information relevant to the fly disease models.

[updated Jul. 2017 by FlyBase; FBrf0222196]

Disease Summary Information
Parent Disease Summary: mitochondrial trifunctional protein deficiency
OMIM report
[MITOCHONDRIAL TRIFUNCTIONAL PROTEIN DEFICIENCY; MTPD](http://omim.org/entry/609015)
Symptoms and phenotype
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 (OMIM:609016), which is caused by mutation in the HADHA gene. [From OMIM:609015, 2016.06.16]
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; OMIM:272120), infantile onset of a hepatic Reye-like syndrome, and late-adolescent onset of primarily a skeletal myopathy (Spiekerkoetter et al., 2003, pubmed:12754706).
Genetics
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 OMIM:609016, 2015.06.16]
Cellular phenotype and pathology
Molecular information
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 OMIM:600890 and OMIM:143450, 2016.06.16]
External links
Disease synonyms
mitochondrial trifunctional protein deficiency; MPTD
MPTD
trifunctional protein deficiency
trifunctional protein deficiency with myopathy and neuropathy
Ortholog Information
Human gene(s) in FlyBase
    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (0)
      Synthetic Gene(s) Used (0)
      Summary of Physical Interactions (0 groups)
      Alleles Reported to Model Human Disease (Disease Ontology) (0 alleles)
      Genetic Tools, Stocks and Reagents
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      Contact lab of origin for a reagent not available from a public stock center.
      Bloomington Stock Center Disease Page
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      RNAi constructs available
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      Selected Drosophila classical alleles
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      References (3)