Trifunctional Protein Deficiency With Myopathy And Neuropathy

An autosomal recessive disorder characterized by decreased activity of 3 mitochondrial enzymes: long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD), long-chain enoyl-CoA hydratase, and long-chain thiolase of the MITOCHONRIAL TRIFUCNTIONAL PROTEIN . Clinically, classic trifunctional protein deficiency can be classified into 3 main clinical phenotypes: neonatal onset of a severe, lethal condition resulting in SUDDEN INFANT DEATH, infantile onset of a hepatic Reye-like syndrome, and late-adolescent onset of primarily a skeletal myopathy. Mutations in the HADHA and HADHB genes have been identified. OMIM: 609015

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Networked: 184 relevant articles (4 outcomes, 16 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Trifunctional Protein Deficiency With Myopathy And Neuropathy
2.	VLCAD deficiency
3.	Medium chain acyl CoA dehydrogenase deficiency
4.	Pregnancy Complications
5.	Maple Syrup Urine Disease

Experts

1.	Spiekerkoetter, Ute: 10 articles (05/2022 - 12/2002)
2.	Gillingham, Melanie B: 8 articles (06/2014 - 06/2003)
3.	Harding, Cary O: 8 articles (06/2014 - 06/2003)
4.	Strauss, Arnold W: 7 articles (01/2016 - 12/2002)
5.	Bennett, M J: 7 articles (01/2013 - 02/2000)
6.	Bennett, Michael J: 7 articles (09/2012 - 05/2003)
7.	Tyni, Tiina: 6 articles (01/2016 - 10/2002)
8.	Wanders, Ronald J A: 6 articles (01/2016 - 01/2002)
9.	Yamaguchi, Seiji: 5 articles (09/2017 - 06/2010)
10.	Strauss, A W: 5 articles (01/2004 - 01/2001)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Trifunctional Protein Deficiency With Myopathy And Neuropathy:

1.	Oxidoreductases (Dehydrogenase)IBA 01/01/2001 - "The diagnosis of long-chain L-3-hydroxy-acyl-coenzyme A dehydrogenase (LCHAD) deficiency frequently requires the study of cultured fibroblasts. " 06/01/2005 - "Long-chain l-3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency has been included in the routine neonatal screening program by the German screening commission. " 02/01/2004 - "The inborn error of metabolism, long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) deficiency, may not be immediately recognizable in the infant. " 06/01/2015 - "Patients with long-chain 3-hydroxy-acyl-CoA dehydrogenase (LCHAD) deficiency commonly present liver dysfunction whose pathogenesis is unknown. " 01/01/2009 - "Acute fatty liver of pregnancy and neonatal long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) deficiency."
2.	Coenzyme A (CoA)IBA 09/01/2012 - "The placenta of an 8-month-old child diagnosed with long-chain 3-hydroxyacyl coenzyme A dehydrogenase (LCHAD) deficiency reportedly showed MFI, but no further evidence of a direct association between MFI/MPVFD and LCHAD deficiency has been documented. " 01/01/2001 - "[Trifunctional protein deficiency and long-chain-3-hydroxy-acyl CoA dehydrogenase deficiency]." 01/01/2012 - "Neonatal screening and earlier diagnosis have improved the prognosis of long-chain 3-hydroxyacyl coenzyme A dehydrogenase (LCHAD) deficiency, which causes a need to refine the staging of the pigmentary chorioretinopathy and thus improve monitoring and comparability of patients under dietary therapy. " 01/01/2007 - "Patients with long-chain 3-hydroxyacyl coenzyme A dehydrogenase (LCHAD) deficiency manifest hypoketotic hypoglycemia, hepatomegaly, hypotonia, lactic acidemia, acute renal failure, cardiomyopathy, and sudden death. " 10/01/2010 - "Only in disorders of the mitochondrial trifunctional protein (TFP) complex, including long-chain 3-hydroxyacyl-coenzyme A (CoA) dehydrogenase (LCHAD) deficiency, neuropathy and retinopathy develop that are progressive and irreversible despite current treatment measures. "
3.	AcidsIBA 01/01/2018 - "They confirm that analyses of acylcarnitines in blood and organic acids in urine alone are not suitable for confirmatory testing and molecular or functional analysis is crucial in diagnosing MTP/LCHAD deficiency. " 01/01/2002 - "Children with LCHAD deficiency are known to excrete 3-hydroxydicarboxylic acids with chain lengths of 10-16 carbons, but a quantitative method to measure excretion of these potentially diagnostically important compounds has not been reported. " 02/01/2000 - "We describe a patient with complex I deficiency who had clinical and biochemical features of long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency including liver failure, cardiomyopathy, and consistent urine organic acid pattern. " 05/01/2003 - "Our results suggest that a medium-chain triglyceride preparation that is higher in decanoate may be more effective in reducing the accumulation of potentially toxic long-chain 3-hydroxy-fatty acids in LCHAD deficiency." 06/01/2003 - "This study reports the relationship of dietary intake and metabolic control as measured by plasma acylcarnitine and organic acid profiles in 10 children with LCHAD or TFP deficiency followed for 1 year. "
4.	BezafibrateIBA 09/01/2020 - "Efficacy of bezafibrate in two patients with mitochondrial trifunctional protein deficiency." 09/01/2020 - "The effectiveness of bezafibrate for FAODs has been reported in some clinical trials, but few clinical studies have investigated its in vivo efficacy toward TFP deficiency. " 01/01/2016 - "Mitochondrial trifunctional protein deficiency in human cultured fibroblasts: effects of bezafibrate." 09/01/2020 - "Our clinical findings indicate that bezafibrate combined with other treatments such as dietary therapy may be effective in improving myopathic manifestations in TFP deficiency."
5.	Triglycerides (Triacylglycerol)IBA 01/01/2003 - "What is the role of medium-chain triglycerides in the management of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency?" 01/01/1996 - "Medium-chain triglyceride loading has no diagnostic power in long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency." 01/01/1991 - "3-Hydroxydicarboxylic aciduria due to long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency associated with sudden neonatal death: protective effect of medium-chain triglyceride treatment." 05/01/2003 - "Our results suggest that a medium-chain triglyceride preparation that is higher in decanoate may be more effective in reducing the accumulation of potentially toxic long-chain 3-hydroxy-fatty acids in LCHAD deficiency." 09/01/2006 - "Metabolic control during exercise with and without medium-chain triglycerides (MCT) in children with long-chain 3-hydroxy acyl-CoA dehydrogenase (LCHAD) or trifunctional protein (TFP) deficiency."
6.	Fatty Acids (Saturated Fatty Acids)IBA 01/01/2012 - "The aim of our study was to evaluate the prevalence of long chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) in the general Estonian population and among patients with symptoms suggestive of fatty acid oxidation (FAO) defects. " 11/01/2011 - "Fibroblast studies in LCHAD deficiency demonstrate that long-chain 3-hydroxy fatty acid accumulation can be observed in cultured tissues. " 04/01/2019 - "Serial fatty acid profiles in a preterm infant with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency." 12/01/2015 - "Trifunctional protein deficiency is a relatively rare disorder of the fatty acid β-oxidation cycle. " 06/01/2015 - "We studied the effects of long-chain 3-hydroxylated fatty acids (LCHFA) that accumulate in LCHAD deficiency on liver bioenergetics using mitochondrial preparations from young rats. "
7.	3-Hydroxyacyl-CoA DehydrogenaseIBA 09/15/1998 - "This study suggests a novel genotype-phenotype correlation in TFP deficiency; that is, mutations in exon 9 of the alpha-subunit, which encodes a linker domain between the NH2-terminal hydratase and the COOH-terminal 3-hydroxyacyl-CoA dehydrogenase, result in a unique neuromuscular phenotype." 08/24/2022 - "Because long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency in the infant can be associated with maternal AFLP, genotyping of the infant was planned. " 01/01/2021 - "Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency and progressive retinopathy: one case report followed by ERGs, VEPs, EOG over a 17-year period." 11/15/2019 - "Evaluation of earlier versus later dietary management in long-chain 3-hydroxyacyl-CoA dehydrogenase or mitochondrial trifunctional protein deficiency: a systematic review." 01/01/2018 - "Patients affected by long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency predominantly present severe liver and cardiac dysfunction, as well as neurological symptoms during metabolic crises, whose pathogenesis is still poorly known. "
8.	Proteins (Proteins, Gene)FDA Link 04/01/1999 - "Evidence that a common mutation in the alpha-subunit (LCHAD) of trifunctional protein, E474Q, is always one of the mutant alleles in fetal isolated LCHAD deficiency associated with these disorders of pregnancy that cause high maternal, fetal, and newborn morbidity and mortality is reviewed. " 09/01/1996 - "We report the molecular defects in a woman with AFLP and her infant who subsequently was diagnosed with trifunctional protein (TFP) deficiency. " 04/01/1994 - "These data suggest a subtle abnormality of trifunctional protein in cells from patient 2. Taken together, the results obtained show that in both patients, long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency is caused by an abnormality in the trifunctional protein, even though there is a heterogeneity in both patients." 01/01/2007 - "Long-term studies are needed to determine whether higher protein diets will reduce the risk of overweight and obesity in children with LCHAD or TFP deficiency." 01/01/2023 - "Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) is a fatty acid oxidation disorder (FAOD) caused by a pathogenic variant, c.1528 G > C, in HADHA encoding the alpha subunit of trifunctional protein (TFPα). "
9.	acylcarnitineIBA 03/01/2017 - "Acylcarnitine analysis demonstrated findings that are consistent with a biochemical diagnosis of LCHAD/TFP deficiency. " 03/01/2017 - "Diagnosis of LCHAD/TFP deficiency in an at risk newborn using umbilical cord blood acylcarnitine analysis." 03/01/2016 - "In the prenatal diagnosis of TFP deficiency, acylcarnitine (AC) analysis has been considered difficult because of limited excretion of long-chain ACs into the fetal urine and hence into the amniotic fluid. " 01/01/2007 - "Their plasma acylcarnitine profiles suggested the presence of LCHAD deficiency by demonstrating highly elevated 3-hydroxyacyl carnitines by tandem mass spectrometry (MS/MS). " 05/01/2006 - "The concentrations of bile long-chain acylcarnitine species analyzed from patients with non-metabolic liver disease were far lower than the levels seen in LCHAD deficiency which also demonstrated a characteristic pattern of 3-hydroxyacylcarnitine excretion. "
10.	Carnitine (L-Carnitine)FDA LinkGeneric 03/01/1999 - "Effects of a low-dose L-carnitine supplement on an adult patient with mitochondrial trifunctional protein deficiency." 05/01/1993 - "Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency--diagnosis, plasma carnitine fractions and management in a further patient." 02/01/2019 - "Although L-carnitine therapy for VLCAD/TFP deficiency has been controversial, supplementation with L-carnitine may be accepted for CPT2/CACT and multiple acyl-CoA dehydrogenase deficiencies. " 06/15/2010 - "Under heat stress (at 41 degrees C), long-chain ACs (C12, C14, or C16) were increased, while medium-chain ACs (C6, C8, or C10) were decreased in cells with carnitine palmitoyl transferase II deficiency, very-long-chain acyl-CoA dehydrogenase deficiency and mitochondrial trifunctional protein deficiency, whereas AC species from short-chain (C4) to long-chain (C16) were barely affected in medium-chain acyl-CoA dehydrogenase and control. " 11/30/1999 - "Conduction disorders and atrial tachycardias were observed in patients with defects of long-chain fatty acid transport across the inner mitochondrial membrane (carnitine palmitoyl transferase type II deficiency and carnitine acylcarnitine translocase deficiency) and in patients with trifunctional protein deficiency. "

Therapies and Procedures

1.	Therapeutics 01/01/2016 - "The neonatal screening and early start of the dietary therapy have improved the outcome of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD). " 06/01/2003 - "Optimal dietary therapy of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency." 09/01/2020 - "Our clinical findings indicate that bezafibrate combined with other treatments such as dietary therapy may be effective in improving myopathic manifestations in TFP deficiency." 12/01/2016 - "Early dietary therapy for long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency can maintain vision despite subnormal retinal function." 09/01/2005 - "Thus, optimal dietary therapy as indicated by low plasma 3-hydroxyacylcarnitine and high plasma DHA concentrations was associated with retention of retinal function and visual acuity in children with LCHAD or TFP deficiency."
2.	Perioperative Period 05/01/2011 - "This case provides instructive information that strict management is needed for patients with trifunctional protein deficiency in the perioperative period."
3.	Physical Therapy Modalities (Physical Therapy Technique) 10/01/2022 - "Effectiveness of Robotic-Assisted Gait Training and Aquatic Physical Therapy in a Child With Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency: A Case Report."
4.	Fat-Restricted Diet (Diet, Fat Restricted) 01/01/2003 - "Plasma and erythrocyte fatty acids have been measured in 9 patients with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency being treated with a low-fat diet. "
5.	Heart Transplantation (Grafting, Heart) 01/01/2018 - "Mitochondrial Trifunctional Protein Deficiency: Severe Cardiomyopathy and Cardiac Transplantation."