Mitochondrial trifunctional protein deficiency

Other names| TFP deficiency[1]
Mitochondrial trifunctional protein deficiency has an autosomal recessive pattern of inheritance
Symptoms| Cardiomyopathy, skeletal myopathy [2]
Types| Mutations in the HADHA and HADHB gene[2]
Diagnostic method| CBC, Urine test[3]
Treatment| Low fat diet, Limited exercise[3]

Mitochondrial trifunctional protein deficiency (MTP deficiency or MTPD) is an autosomal recessive fatty acid oxidation disorder[4] that prevents the body from converting certain fats to energy, particularly during periods without food.[5][6]

People with this disorder have inadequate levels of an enzyme that breaks down a certain group of fats called long-chain fatty acids.[6]

## Contents

* 1 Signs and symptoms
* 2 Genetics
* 3 Diagnosis
* 4 Treatment
* 5 See also
* 6 References
* 7 Further reading
* 8 External links

## Signs and symptoms

The presentation of mitochondrial trifunctional protein deficiency may begin during infancy, features that occur are: low blood sugar, weak muscle tone, and liver problems. Infants with this disorder are at risk for heart problems, breathing difficulties, and pigmentary retinopathy. Signs and symptoms of mitochondrial trifunctional protein deficiency that may begin after infancy include hypotonia, muscle pain, a breakdown of muscle tissue, and a loss of sensation in the extremities called peripheral neuropathy. Some who have MTP deficiency show a progressive course associated with myopathy, and recurrent rhabdomyolysis.[2][6][7]

## Genetics

HADHB function in beta-oxidation

The genetics of mitochondrial trifunctional protein deficiency is based on mutations in the HADHA[8] and HADHB[9] genes which cause this disorder. These genes each provide instructions for making part of an enzyme complex called mitochondrial trifunctional protein. This enzyme complex functions in mitochondria, the energy-producing centers within cells: mitochondrial trifunctional protein contains three enzymes that each perform a different function. This enzyme complex is required to metabolize a group of fats called long-chain fatty acids. These fatty acids are stored in the body's fat tissues and are a major source of energy for the heart and muscles. During periods of fasting, fatty acids are also an important energy source for the liver and other tissues.[10][11][12]

Mutations in the HADHA or HADHB genes that cause mitochondrial trifunctional protein deficiency disrupt all functions of this enzyme complex.[13] Without enough of this enzyme complex, long-chain fatty acids cannot be metabolized. As a result, these fatty acids are not converted to energy, which can lead to some features of this disorder. Long-chain fatty acids may also build up and damage the liver, heart, and muscles. This abnormal buildup causes other symptoms of mitochondrial trifunctional protein deficiency.

The mechanism of this condition indicates that the mitochondrial trifunction protein 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, trifunctional protein deficiency usually results in sudden unexplained infant death, cardiomyopathy, or skeletal myopathy.[14][11][12]

## Diagnosis

Diagnosis of mitochondrial trifunctional protein deficiency is often confirmed using tandem mass spectrometry.[4] Genetic counseling is available for this condition. Additionally the following exams are available:

* CBC[3]
* Urine test[3]

## Treatment

Glucose.

Management for mitochondrial trifunctional protein deficiency entails the following:[7]

* Avoiding factors that might precipitate condition
* Glucose
* Low fat/high carbohydrate nutrition

## See also

* Long-chain acyl-CoA dehydrogenase

## References

1. ↑ "Mitochondrial trifunctional protein deficiency | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". https://rarediseases.info.nih.gov/diseases/3684/index.
2. ↑ 2.0 2.1 2.2 "Mitochondrial trifunctional protein deficiency | Genetic and Rare Diseases Information Center(GARD) – an NCATS Program". https://rarediseases.info.nih.gov/diseases/3684/mitochondrial-trifunctional-protein-deficiency.
3. ↑ 3.0 3.1 3.2 3.3 RESERVED, INSERM US14 -- ALL RIGHTS. "Orphanet: Mitochondrial trifunctional protein deficiency". http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=746.
4. ↑ 4.0 4.1 "Management of fatty acid oxidation disorders: a survey of current treatment strategies". J Am Diet Assoc 102 (12): 1800–1803. 2002. doi:10.1016/S0002-8223(02)90386-X. PMID 12487544. subscription needed
5. ↑ "OMIM Entry - # 609015 - MITOCHONDRIAL TRIFUNCTIONAL PROTEIN DEFICIENCY; MTPD". http://omim.org/entry/609015.
6. ↑ 6.0 6.1 6.2 Reference, Genetics Home. "mitochondrial trifunctional protein deficiency". https://medlineplus.gov/genetics/condition/mitochondrial-trifunctional-protein-deficiency/.
7. ↑ 7.0 7.1 Swaiman, Kenneth F.; Ashwal, Stephen; Ferriero, Donna M.; Schor, Nina F. (2014) (in en). Swaiman's Pediatric Neurology: Principles and Practice. Elsevier Health Sciences. pp. 461, 1638. ISBN 978-0323089111. https://books.google.com/books?id=bonlLHarTFAC&dq=Mitochondrial+trifunctional+protein+deficiency+signs&pg=PA461. Retrieved 12 November 2016.
8. ↑ Reference, Genetics Home. "HADHA gene". https://medlineplus.gov/genetics/gene/hadha/.
9. ↑ Reference, Genetics Home. "HADHB gene". https://medlineplus.gov/genetics/gene/hadhb.
10. ↑ "Long-Chain Acyl CoA Dehydrogenase Deficiency: Background, Pathophysiology, Epidemiology". 24 March 2016. http://emedicine.medscape.com/article/945857-overview#showall.
11. ↑ 11.0 11.1 "HADHA hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase (trifunctional protein), alpha subunit [Homo sapiens (human) \- Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/3030.
12. ↑ 12.0 12.1 "Home - Gene - NCBI". https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=3032.
13. ↑ "OMIM Entry - * 600890 - HYDROXYACYL-CoA DEHYDROGENASE/3-KETOACYL-CoA THIOLASE/ENOYL-CoA HYDRATASE, ALPHA SUBUNIT; HADHA". http://omim.org/entry/600890.
14. ↑ Rector, R. Scott; Payne, R. Mark; Ibdah, Jamal A. (1 January 2008). "Mitochondrial Trifunctional Protein Defects: Clinical Implications and Therapeutic Approaches". Adv Drug Deliv Rev 60 (13–14): 1488–1496. doi:10.1016/j.addr.2008.04.014. ISSN 0169-409X. PMID 18652860.

## Further reading

* Nyhan, William L.; Hoffman, Georg F.; Barshop, Bruce A.; Al-Aqeel, Aida I. (2012) (in en). Atlas of Inherited Metabolic Diseases 3E. CRC Press. ISBN 9781444149487. https://books.google.com/books?id=vCvSBQAAQBAJ&q=Mitochondrial+trifunctional+protein+deficiency+signs.
* Thöny, Beat; Duran, Marinus; Gibson, K. Michael; Dionisi-Vici, Carlo (2013) (in en). Physician's Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases. Springer. ISBN 9783642403378. https://books.google.com/books?id=t9i6BQAAQBAJ&dq=Mitochondrial+trifunctional+protein+deficiency+treatment&pg=PR39.

## External links

Classification|

* OMIM: 609015
* MeSH: D024741
* DiseasesDB: 34111

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External resources|

* eMedicine: ped/1284
* Orphanet: 746

| Wikimedia Commons has media related to Mitochondrial trifunctional protein deficiency.

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Inborn error of lipid metabolism: fatty-acid metabolism disorders (E71.3, 277.81–277.85)

Synthesis|

* Biotinidase deficiency (BTD)

Degradation|

| Acyl
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* Carnitine
* CPT1
* CPT2
* CDSP
* CACTD
* Adrenoleukodystrophy (ALD)

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Beta
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* Acyl CoA dehydrogenase
* Short-chain SCADD
* Medium-chain MCADD
* Long-chain 3-hydroxy LCHAD
* Very long-chain VLCADD

* Mitochondrial trifunctional protein deficiency (MTPD): Acute fatty liver of pregnancy]]

|

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* 2,4 Dienoyl-CoA reductase deficiency (DECRD)

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Other|

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