Mitochondrial trifunctional protein deficiency

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.{{Cite web |title=Mitochondrial trifunctional protein deficiency {{!}} Genetic and Rare Diseases Information Center(GARD) – an NCATS Program |url=https://rarediseases.info.nih.gov/diseases/3684/mitochondrial-trifunctional-protein-deficiency |url-status=live |archive-url=https://web.archive.org/web/20190109063929/https://rarediseases.info.nih.gov/diseases/3684/mitochondrial-trifunctional-protein-deficiency |archive-date=9 January 2019 |access-date=12 November 2016 |website=rarediseases.info.nih.gov}}{{Cite book |last=Swaiman |first=Kenneth F. |url=https://books.google.com/books?id=bonlLHarTFAC&dq=Mitochondrial+trifunctional+protein+deficiency+signs&pg=PA461 |title=Swaiman's Pediatric Neurology: Principles and Practice |last2=Ashwal |first2=Stephen |last3=Ferriero |first3=Donna M. |author-link3=Donna Ferriero |last4=Schor |first4=Nina F. |date=2014 |publisher=Elsevier Health Sciences |isbn=978-0323089111 |pages=461, 1638 |language=en |accessdate=12 November 2016}}

File:Beta-ketothiolase.png]]

The genetics of mitochondrial trifunctional protein deficiency is based on mutations in the HADHA{{Cite web |last=Reference |first=Genetics Home |title=HADHA gene |url=https://ghr.nlm.nih.gov/gene/HADHA#conditions |url-status=live |archive-url=https://web.archive.org/web/20191017205033/https://ghr.nlm.nih.gov/gene/HADHA#conditions |archive-date=2019-10-17 |access-date=2016-11-05 |website=Genetics Home Reference}} and HADHB{{Cite web |last=Reference |first=Genetics Home |title=HADHB gene |url=https://ghr.nlm.nih.gov/gene/HADHB |url-status=live |archive-url=https://web.archive.org/web/20161105160942/https://ghr.nlm.nih.gov/gene/HADHB |archive-date=2016-11-05 |access-date=2016-11-05 |website=Genetics Home Reference}} 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.{{Cite web |date=24 March 2016 |title=Long-Chain Acyl CoA Dehydrogenase Deficiency: Background, Pathophysiology, Epidemiology |url=http://emedicine.medscape.com/article/945857-overview#showall |url-status=live |archive-url=https://web.archive.org/web/20200313085833/https://emedicine.medscape.com/article/945857-overview#showall |archive-date=13 March 2020 |access-date=12 November 2016 |website=eMedicine}}{{Cite web |title=HADHA hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase (trifunctional protein), alpha subunit [Homo sapiens (human)] - Gene - NCBI |url=https://www.ncbi.nlm.nih.gov/gene/3030 |url-status=live |archive-url=https://web.archive.org/web/20180825041331/https://www.ncbi.nlm.nih.gov/gene/3030 |archive-date=25 August 2018 |access-date=12 November 2016 |website=www.ncbi.nlm.nih.gov}}{{Cite web |title=Home - Gene - NCBI |url=https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=3032 |url-status=live |archive-url=https://web.archive.org/web/20161113060727/https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=3032 |archive-date=13 November 2016 |access-date=12 November 2016 |website=www.ncbi.nlm.nih.gov}}

Mutations in the HADHA or HADHB genes that cause mitochondrial trifunctional protein deficiency disrupt all functions of this enzyme complex.{{Cite web |title=OMIM Entry - * 600890 - HYDROXYACYL-CoA DEHYDROGENASE/3-KETOACYL-CoA THIOLASE/ENOYL-CoA HYDRATASE, ALPHA SUBUNIT; HADHA |url=http://omim.org/entry/600890 |url-status=live |archive-url=https://web.archive.org/web/20150731124948/http://omim.org/entry/600890 |archive-date=31 July 2015 |access-date=5 November 2016 |website=omim.org}} 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.{{medical citation needed|date=November 2016}}

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.{{Cite journal |last=Rector |first=R. Scott |last2=Payne |first2=R. Mark |last3=Ibdah |first3=Jamal A. |date=1 January 2008 |title=Mitochondrial Trifunctional Protein Defects: Clinical Implications and Therapeutic Approaches |journal=Adv Drug Deliv Rev |volume=60 |issue=13–14 |pages=1488–1496 |doi=10.1016/j.addr.2008.04.014 |issn=0169-409X |pmc=2848452 |pmid=18652860}}

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

• CBC{{Cite web |last=RESERVED |first=INSERM US14 -- ALL RIGHTS |title=Orphanet: Mitochondrial trifunctional protein deficiency |url=http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=746 |url-status=live |archive-url=https://web.archive.org/web/20161113114117/http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=746 |archive-date=2016-11-13 |access-date=2016-11-12 |website=www.orpha.net}}
• Urine test

Image:Glucose Fisher to Haworth.gif

Management for mitochondrial trifunctional protein deficiency entails the following:

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

• Long-chain acyl-CoA dehydrogenase

{{Reflist}}

• {{Cite book |last=Nyhan |first=William L. |url=https://books.google.com/books?id=vCvSBQAAQBAJ&q=Mitochondrial+trifunctional+protein+deficiency+signs |title=Atlas of Inherited Metabolic Diseases 3E |last2=Hoffman |first2=Georg F. |last3=Barshop |first3=Bruce A. |last4=Al-Aqeel |first4=Aida I. |date=2012 |publisher=CRC Press |isbn=9781444149487 |language=en}}
• {{Cite book |last=Thöny |first=Beat |url=https://books.google.com/books?id=t9i6BQAAQBAJ&dq=Mitochondrial+trifunctional+protein+deficiency+treatment&pg=PR39 |title=Physician's Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases |last2=Duran |first2=Marinus |last3=Gibson |first3=K. Michael |last4=Dionisi-Vici |first4=Carlo |date=2013 |publisher=Springer |isbn=9783642403378 |language=en}}

• {{Commons category-inline}}

{{Medical resources

| DiseasesDB = 34111

| ICD10 =

| ICD9 =

| ICDO =

| OMIM = 609015

| MedlinePlus =

| eMedicineSubj = ped

| eMedicineTopic = 1284

| MeshID = D024741

| Orphanet = 746

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{{Commons}}

{{Scholia|topic}}

{{Fatty-acid metabolism disorders}}

{{Medicine}}

Category:Autosomal recessive disorders

Category:Fatty-acid metabolism disorders