MTPD
MCID: MTC027
MIFTS: 58

Mitochondrial Trifunctional Protein Deficiency (MTPD)

Categories: Genetic diseases, Metabolic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Mitochondrial Trifunctional Protein Deficiency

MalaCards integrated aliases for Mitochondrial Trifunctional Protein Deficiency:

Name: Mitochondrial Trifunctional Protein Deficiency 56 12 74 52 25 58 73 36 29 6 15 39
Tfp Deficiency 12 52 25 58
Trifunctional Protein Deficiency with Myopathy and Neuropathy 73 43 71
Trifunctional Protein Deficiency 56 73 13
Mtpd 56 12 73
Tfpd 12 58
Trifunctional Protein Deficiency, Type 2 25
Abetalipoproteinemia 71
Mtp Deficiency 25
Tpa Deficiency 25

Characteristics:

Orphanet epidemiological data:

58
mitochondrial trifunctional protein deficiency
Inheritance: Autosomal recessive; Prevalence: 1-9/100000 (Europe); Age of onset: Infancy,Neonatal; Age of death: early childhood;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
sudden infant death may occur
three major clinical forms are apparent
rapidly progressive neonatal onset with early death
infantile onset with hepatic involvement
childhood or adolescent onset, protracted, with myopathy and neuropathy
symptoms may be aggravated by acute illness
most patients die from heart failure


HPO:

31
mitochondrial trifunctional protein deficiency:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


Summaries for Mitochondrial Trifunctional Protein Deficiency

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 746 Definition A rare disorder of fatty acid oxidation characterized by a wide clinical spectrum ranging from severe neonatal manifestations including cardiomyopathy , hypoglycemia , metabolic acidosis, skeletal myopathy and neuropathy, liver disease and death to a mild phenotype with peripheral polyneuropathy, episodic rhabdomyolysis and pigmentary retinopathy.. Epidemiology TFPD has been reported in less than 100 cases in the literature. Clinical description The neonatal onset, severe form manifests as hepatic steatosis, cardiomyopathy, skeletal myopathy and neuropathy and is usually fatal. A moderately severe form, with onset usually from the neonatal period to 18 months of age, presents primarily with hypoketotic hypoglycemia and metabolic acidosis which is often precipitated by prolonged fasting and/or intercurrent illness. Both forms can manifest with neuropathy with or without cardiomyopathy and can be fatal. The mild form merges with the moderately severe infantile form and can present from a few months of age until adolescence as a peripheral polyneuropathy with episodic rhabdomyolysis triggered by prolonged fasting, illness, exercise or exposure to heat or cold. There is respiratory failure associated with the episodes of rhabdomyolysis. A pigmentary retinopathy may also develop over time. Very occasionally, adults presenting for the first time with a previously unrecognized disease are described. Etiology The TFP, composed of 4 alpha and 4 beta subunits, catalyzes 3 steps in mitochondrial beta-oxidation of fatty acids which are the long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD), long-chain enoyl-CoA hydratase (LCEH), and long-chain thiolase (LCTH) steps. The HADHA gene (2p23) encodes the LCEH and LCHAD enzymes and the HADHB gene (2p23) encodes the LCTH enzyme. Two mutations in either one of these two genes causes TFPD. Diagnostic methods Urine organic acids may show a C6-C14 (hydroxy) dicarboxylic aciduria, and blood acylcarnitine analysis often shows increased long chain hydroxyacyl carnitine species (C14-OH, C16-OH, C18-OH, C18:1-OH). Both urine and blood markers are less reliable and more variable than those seen in LCHAD deficiency (see this term). This is because defects in LCEH may block the formation of hydroxy-metabolites. Reduced enzyme activity in at least two (usually all 3) enzymes in cultured fibroblasts is seen. Molecular analysis confirming bi-allelic non-1528C>G mutations in the HADHA gene or bi-allelic mutations in the HADHB gene confirms diagnosis. Newborn screening is available in Austria, Czech Republic, Denmark, Germany, Hungary, Iceland, Netherlands and Portugal. Differential diagnosis Sudden infant death syndrome and isolated LCHAD deficiency (see this term) form part of the differential diagnosis. LCHAD deficiency is clinically indistinguishable from severe TFPD. Antenatal diagnosis Prenatal diagnosis is possible by analyzing enzyme activity in chorionic villi samples, once a deficiency of TFP has been established in the index case/family. Molecular analysis is the preferred option when two mutations have been identified in a family. Genetic counseling TFPD is an autosomal recessive disorder and genetic counseling is possible. Management and treatment Treatment involves adherence to a low fat diet with restriction of long chain fatty acid intake and substitution with medium chain fatty acids. Fasting and exposure to environmental extremes must be strictly avoided and exercise should be limited. Prognosis Prognosis for the severe neonatal form of TFPD is very poor. The later onset mild form has a far more favorable prognosis. Visit the Orphanet disease page for more resources.

MalaCards based summary : Mitochondrial Trifunctional Protein Deficiency, also known as tfp deficiency, is related to encephalopathy, progressive, early-onset, with episodic rhabdomyolysis and abetalipoproteinemia, and has symptoms including ataxia, myalgia and weakness. An important gene associated with Mitochondrial Trifunctional Protein Deficiency is HADHA (Hydroxyacyl-CoA Dehydrogenase Trifunctional Multienzyme Complex Subunit Alpha), and among its related pathways/superpathways are Fatty acid degradation and Fatty acid metabolism. The drugs carnitine and Tocopherol have been mentioned in the context of this disorder. Affiliated tissues include liver, heart and retina, and related phenotypes are areflexia and exercise intolerance

Disease Ontology : 12 A lipid metabolism disorder characterized by abnormal fatty acid oxidation resulting a wide range of clinical manifestations from servere neonatal symptoms including cardiomyopathy, hypoglycemia, metabolic acidosis, skeletal myopathy and neuropathy, liver disease and death to a more mild phenotype including peripheral polyneuropathy, episodic rhabdomyolysis and pigmentary retinopathy that has material basis in homozygous or compound heterozygous mutation in either of the subunits of the mitochondrial trifunctional protein; HADHA or HADHB on 2p23.3.

Genetics Home Reference : 25 Mitochondrial trifunctional protein deficiency is a rare condition that prevents the body from converting certain fats to energy, particularly during periods without food (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, lack of energy (lethargy), low blood sugar (hypoglycemia), weak muscle tone (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 a loss of sensation in the extremities (peripheral neuropathy). Problems related to mitochondrial trifunctional protein deficiency can be triggered by periods of fasting or by illnesses such as viral infections. This disorder is sometimes mistaken for Reye syndrome, a severe disorder that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.

OMIM : 56 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; 272120), infantile onset of a hepatic Reye-like syndrome, and late-adolescent onset of primarily a skeletal myopathy (Spiekerkoetter et al., 2003). 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). See also isolated LCHAD deficiency (609016), which is caused by mutation in the HADHA gene. (609015)

KEGG : 36 Mitochondrial trifunctional protein (TFP) deficiency is a rare autosomal recessive disorder that is caused by mutations in HADHA and HADHB. TFP is a multienzyme complex of the fatty acid beta-oxidation cycle. Human TFP is an octamer composed of four alpha-subunits harboring long-chain enoyl-CoA hydratase and long-chain L-3-hydroxyacyl-CoA dehydrogenase (LCHAD) and four beta-subunits encoding long-chain 3-ketoacyl-CoA thiolase (LCKAT). This disease includes a lethal neonatal phenotype with cardiomyopathy and Reye-like syndrome, an infantile hepatic phenotype with recurrent hypoketotic hypoglycemia, and a childhood or adolescent-onset neuromyopathic phenotype with peripheral neuropathy and recurrent rhabdomyolysis.

UniProtKB/Swiss-Prot : 73 Mitochondrial trifunctional protein deficiency: A disease biochemically characterized by loss of all enzyme activities of the mitochondrial trifunctional protein complex. Variable clinical manifestations include hypoglycemia, cardiomyopathy, delayed psychomotor development, sensorimotor axonopathy, generalized weakness, hepatic dysfunction, respiratory failure. Sudden infant death may occur. Most patients die from heart failure.

Wikipedia : 74 Mitochondrial trifunctional protein deficiency (MTP deficiency or MTPD) is an autosomal recessive fatty... more...

Related Diseases for Mitochondrial Trifunctional Protein Deficiency

Diseases related to Mitochondrial Trifunctional Protein Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 73)
# Related Disease Score Top Affiliating Genes
1 encephalopathy, progressive, early-onset, with episodic rhabdomyolysis 31.2 CPT2 ACADVL
2 abetalipoproteinemia 30.5 HADHB HADHA CPT2
3 atrial standstill 1 30.3 SLC25A20 HADHA CPT2 ACADVL
4 long-chain 3-hydroxyacyl-coa dehydrogenase deficiency 30.2 HADHA HADH GAREM2 ACADVL ACADM
5 myoglobinuria 30.0 HADH ETFDH CPT2 ACADVL
6 3-hydroxyacyl-coa dehydrogenase deficiency 29.9 HADHA HADH GAREM2 ACADVL ACADM
7 acyl-coa dehydrogenase deficiency 29.4 HADHA ETFDH ACADVL ACADS ACADM
8 hypoglycemia 29.4 SLC25A20 HADHB HADHA HADH CPT2 ACADVL
9 myopathy 28.8 SLC25A20 HADHA HADH ETFDH CPT2 ACADVL
10 acyl-coa dehydrogenase, very long-chain, deficiency of 28.0 SLC25A20 HADHB HADHA HADH ETFDH CPT2
11 peripheral nervous system disease 10.5
12 neuropathy 10.5
13 autosomal recessive disease 10.4
14 inherited metabolic disorder 10.4
15 hypoparathyroidism 10.3
16 polyneuropathy 10.3
17 myoglobinuria, recurrent 10.3 CPT2 ACADVL
18 fatty liver disease 10.2
19 hypotonia 10.2
20 muscular lipidosis 10.2 ETFDH ACADS
21 complement component 2 deficiency 10.1 HADHA ACADVL
22 isovaleric acidemia 10.1 HADHA ACADVL ACADS
23 enterocolitis 10.1
24 ataxia and polyneuropathy, adult-onset 10.1
25 metabolic acidosis 10.1
26 charcot-marie-tooth disease 10.1
27 tooth disease 10.1
28 hemopericardium 10.1
29 pericardial effusion 10.1
30 hypertrophic cardiomyopathy 10.1
31 hellp syndrome 10.1
32 diarrhea 10.1
33 acute kidney failure 10.1
34 vaccinia 10.1
35 lactic acidosis 10.1
36 pulmonary fibrosis 10.1
37 axonal neuropathy 10.1
38 placenta disease 10.1
39 perinatal necrotizing enterocolitis 10.1
40 bacterial pneumonia 10.1
41 retinoschisis 1, x-linked, juvenile 10.1
42 joint laxity, short stature, and myopia 10.1
43 myopia 10.1
44 macular holes 10.1
45 disorder of fatty acid oxidation and ketogenesis 10.1
46 d-bifunctional protein deficiency 10.0 HADHB HADH EHHADH
47 carnitine-acylcarnitine translocase deficiency 10.0 SLC25A20 HADHA CPT2 ACADVL
48 sudden infant death syndrome 10.0
49 hepatic coma 10.0
50 hepatic encephalopathy 10.0

Graphical network of the top 20 diseases related to Mitochondrial Trifunctional Protein Deficiency:



Diseases related to Mitochondrial Trifunctional Protein Deficiency

Symptoms & Phenotypes for Mitochondrial Trifunctional Protein Deficiency

Human phenotypes related to Mitochondrial Trifunctional Protein Deficiency:

58 31 (show top 50) (show all 60)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 areflexia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001284
2 exercise intolerance 58 31 hallmark (90%) Very frequent (99-80%) HP:0003546
3 rhabdomyolysis 58 31 hallmark (90%) Very frequent (99-80%) HP:0003201
4 muscular hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0001252
5 congestive heart failure 58 31 frequent (33%) Frequent (79-30%) HP:0001635
6 failure to thrive in infancy 58 31 frequent (33%) Frequent (79-30%) HP:0001531
7 left ventricular hypertrophy 58 31 frequent (33%) Frequent (79-30%) HP:0001712
8 hypocalcemia 58 31 frequent (33%) Frequent (79-30%) HP:0002901
9 lethargy 58 31 frequent (33%) Frequent (79-30%) HP:0001254
10 cardiomyopathy 58 31 frequent (33%) Frequent (79-30%) HP:0001638
11 poor suck 58 31 frequent (33%) Frequent (79-30%) HP:0002033
12 muscle spasm 58 31 frequent (33%) Frequent (79-30%) HP:0003394
13 chronic hepatic failure 58 31 frequent (33%) Frequent (79-30%) HP:0100626
14 lower limb muscle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0007340
15 difficulty climbing stairs 58 31 frequent (33%) Frequent (79-30%) HP:0003551
16 hypoketotic hypoglycemia 58 31 frequent (33%) Frequent (79-30%) HP:0001985
17 diffuse hepatic steatosis 58 31 frequent (33%) Frequent (79-30%) HP:0006555
18 decreased patellar reflex 58 31 frequent (33%) Frequent (79-30%) HP:0011808
19 progressive distal muscle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0009063
20 skeletal myopathy 58 31 frequent (33%) Frequent (79-30%) HP:0003756
21 generalized muscle weakness 58 31 occasional (7.5%) Occasional (29-5%) HP:0003324
22 arrhythmia 58 31 occasional (7.5%) Occasional (29-5%) HP:0011675
23 myalgia 58 31 occasional (7.5%) Occasional (29-5%) HP:0003326
24 toe walking 58 31 occasional (7.5%) Occasional (29-5%) HP:0040083
25 motor delay 58 31 occasional (7.5%) Occasional (29-5%) HP:0001270
26 mitral regurgitation 58 31 occasional (7.5%) Occasional (29-5%) HP:0001653
27 hypoparathyroidism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000829
28 pes cavus 58 31 occasional (7.5%) Occasional (29-5%) HP:0001761
29 cholestasis 58 31 occasional (7.5%) Occasional (29-5%) HP:0001396
30 babinski sign 58 31 occasional (7.5%) Occasional (29-5%) HP:0003487
31 respiratory failure 58 31 occasional (7.5%) Occasional (29-5%) HP:0002878
32 tricuspid regurgitation 58 31 occasional (7.5%) Occasional (29-5%) HP:0005180
33 pigmentary retinopathy 58 31 very rare (1%) Occasional (29-5%) HP:0000580
34 frequent falls 58 31 occasional (7.5%) Occasional (29-5%) HP:0002359
35 coma 58 31 occasional (7.5%) Occasional (29-5%) HP:0001259
36 equinovarus deformity 58 31 occasional (7.5%) Occasional (29-5%) HP:0008110
37 equinus calcaneus 58 31 occasional (7.5%) Occasional (29-5%) HP:0008138
38 seizure 31 occasional (7.5%) HP:0001250
39 sensorimotor neuropathy 58 31 very rare (1%) Very rare (<4-1%) HP:0007141
40 primitive reflex 58 31 very rare (1%) Very rare (<4-1%) HP:0002476
41 distal peripheral sensory neuropathy 58 31 very rare (1%) Very rare (<4-1%) HP:0007067
42 rigors 58 31 very rare (1%) Very rare (<4-1%) HP:0025145
43 peripheral neuropathy 58 31 Frequent (79-30%) HP:0009830
44 respiratory insufficiency 58 31 Occasional (29-5%) HP:0002093
45 global developmental delay 31 HP:0001263
46 seizures 58 Occasional (29-5%)
47 feeding difficulties in infancy 58 Frequent (79-30%)
48 muscle weakness 58 Frequent (79-30%)
49 failure to thrive 31 HP:0001508
50 myopathy 31 HP:0003198

Symptoms via clinical synopsis from OMIM:

56
Growth Other:
failure to thrive
small for gestational age

Cardiovascular Heart:
dilated cardiomyopathy
cardiac failure
low-output cardiomyopathy

Respiratory:
respiratory failure

Neurologic Central Nervous System:
delayed psychomotor development
poor spontaneous movements

Head And Neck Eyes:
pigmentary retinopathy (rare)

Metabolic Features:
lactic acidosis endocrine : hypoparathyroidism (in some patients)

Prenatal Manifestations Amniotic Fluid:
hydrops fetalis

Laboratory Abnormalities:
hyperammonemia
hypoketotic hypoglycemia
myoglobinuria
abnormal liver enzymes
decreased activity of long-chain 3-hydroxyacyl-coa dehydrogenase, long-chain 3-oxoacyl-coa thiolase, and long-chain 2-enoyl-coa hydratase
more
Muscle Soft Tissue:
muscle pain
hypotonia
generalized weakness
limb-girdle myopathy, slowly progressive
rhabdomyolysis, episodic

Abdomen Liver:
hepatic dysfunction

Neurologic Peripheral Nervous System:
sensorimotor axonopathy

Prenatal Manifestations Maternal:
hellp syndrome (hemolysis, elevated liver enzymes, low platelets)

Clinical features from OMIM:

609015

UMLS symptoms related to Mitochondrial Trifunctional Protein Deficiency:


ataxia, myalgia, weakness

MGI Mouse Phenotypes related to Mitochondrial Trifunctional Protein Deficiency:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 9.7 ACADM ACADS ACADVL CPT2 EHHADH HADH
2 liver/biliary system MP:0005370 9.17 ACADM ACADS ACADVL EHHADH HADHA HADHB

Drugs & Therapeutics for Mitochondrial Trifunctional Protein Deficiency

Drugs for Mitochondrial Trifunctional Protein Deficiency (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 15)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1 carnitine Phase 2
2
Tocopherol Approved, Investigational 1406-66-2, 54-28-4 14986
3
Vitamin A Approved, Nutraceutical, Vet_approved 22737-96-8, 68-26-8, 11103-57-4 9904001 445354
4
Vitamin E Approved, Nutraceutical, Vet_approved 59-02-9 14985
5 Tocotrienol Investigational 6829-55-6
6 retinol
7 Retinol palmitate
8 Micronutrients
9 Trace Elements
10 Vitamins
11 Antioxidants
12 Nutrients
13 Tocopherols
14 Tocotrienols
15 Protective Agents

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 An Open-label Long-Term Safety and Efficacy Extension Study in Subjects With Long-Chain Fatty Acid Oxidation Disorders (LC-FAOD) Previously Enrolled in UX007 or Triheptanoin Studies Enrolling by invitation NCT02214160 Phase 2 UX007
2 Fatty Acid Oxidation Disorders & Body Weight Regulation Completed NCT00654004
3 Vitamin Replacement in Abetalipoproteinemia Completed NCT00004574
4 Foundation Fighting Blindness Registry, My Retina Tracker Recruiting NCT02435940
5 UX007-EAP101: An Open-label Intermediate-size Treatment Protocol for the Urgent Treatment of Seriously Ill Patients With Long-Chain Fatty Acid Oxidation Disorders (LC-FAOD) With Triheptanoin (UX007). // UX007G-EAP102: An Open-label Intermediate-size Treatment Protocol for the Urgent Treatment of Seriously Ill Patients With Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS) With Triheptanoin (UX007) Available NCT03773770 Triheptanoin
6 Vitamin E Treatment for LCHAD Associated Neuropathy Terminated NCT00840112

Search NIH Clinical Center for Mitochondrial Trifunctional Protein Deficiency

Cochrane evidence based reviews: trifunctional protein deficiency with myopathy and neuropathy

Genetic Tests for Mitochondrial Trifunctional Protein Deficiency

Genetic tests related to Mitochondrial Trifunctional Protein Deficiency:

# Genetic test Affiliating Genes
1 Mitochondrial Trifunctional Protein Deficiency 29 HADHA HADHB

Anatomical Context for Mitochondrial Trifunctional Protein Deficiency

MalaCards organs/tissues related to Mitochondrial Trifunctional Protein Deficiency:

40
Liver, Heart, Retina

Publications for Mitochondrial Trifunctional Protein Deficiency

Articles related to Mitochondrial Trifunctional Protein Deficiency:

(show top 50) (show all 89)
# Title Authors PMID Year
1
Mitochondrial trifunctional protein deficiency: a rare cause of adult-onset rhabdomyolysis. 61 56 6
23868323 2013
2
Clinical and molecular aspects of Japanese patients with mitochondrial trifunctional protein deficiency. 56 6 61
19699128 2009
3
Two novel HADHB gene mutations in a Korean patient with mitochondrial trifunctional protein deficiency. 56 6 61
19880769 2009
4
Mild trifunctional protein deficiency is associated with progressive neuropathy and myopathy and suggests a novel genotype-phenotype correlation. 6 61 56
9739053 1998
5
Molecular characterization of mitochondrial trifunctional protein deficiency: formation of the enzyme complex is important for stabilization of both alpha- and beta-subunits. 61 56 6
8651282 1996
6
Mutations in HADHB, which encodes the β-subunit of mitochondrial trifunctional protein, cause infantile onset hypoparathyroidism and peripheral polyneuropathy. 56 6
24664533 2014
7
Genomic and mutational analysis of the mitochondrial trifunctional protein beta-subunit (HADHB) gene in patients with trifunctional protein deficiency. 56 6
9259266 1997
8
Two alpha subunit donor splice site mutations cause human trifunctional protein deficiency. 56 6
7738175 1995
9
Progressive neuropathy and recurrent myoglobinuria in a child with long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency. 56 6
2019931 1991
10
Molecular and phenotypic heterogeneity in mitochondrial trifunctional protein deficiency due to beta-subunit mutations. 61 56
12754706 2003
11
Mitochondrial trifunctional protein deficiency: a severe fatty acid oxidation disorder with cardiac and neurologic involvement. 61 56
12838198 2003
12
Mitochondrial trifunctional protein deficiency associated with recurrent myoglobinuria in adolescence. 56 61
9305349 1997
13
Maternal acute fatty liver of pregnancy associated with fetal trifunctional protein deficiency: molecular characterization of a novel maternal mutant allele. 61 6
8865274 1996
14
Hypoparathyroidism in mitochondrial trifunctional protein deficiency. 56 61
8757579 1996
15
Mitochondrial trifunctional protein deficiency. Catalytic heterogeneity of the mutant enzyme in two patients. 61 6
8163672 1994
16
Trifunctional protein deficiency: three families with significant maternal hepatic dysfunction in pregnancy not associated with E474Q mutation. 56
11196108 2000
17
Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: variable expressivity of maternal illness during pregnancy and unusual presentation with infantile cholestasis and hypocalcaemia. 6
10518281 1999
18
A fetal fatty-acid oxidation disorder as a cause of liver disease in pregnant women. 56
10352164 1999
19
Molecular basis of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: identification of two new mutations. 6
9266371 1997
20
Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency with the G1528C mutation: clinical presentation of thirteen patients. 6
9003853 1997
21
Trifunctional enzyme deficiency: adult presentation of a usually fatal beta-oxidation defect. 56
8871579 1996
22
Common missense mutation G1528C in long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency. Characterization and expression of the mutant protein, mutation analysis on genomic DNA and chromosomal localization of the mitochondrial trifunctional protein alpha subunit gene. 6
8770876 1996
23
The molecular basis of pediatric long chain 3-hydroxyacyl-CoA dehydrogenase deficiency associated with maternal acute fatty liver of pregnancy. 6
7846063 1995
24
Molecular basis of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: identification of the major disease-causing mutation in the alpha-subunit of the mitochondrial trifunctional protein. 6
7811722 1994
25
Human trifunctional protein deficiency: a new disorder of mitochondrial fatty acid beta-oxidation. 56
1445348 1992
26
Combined enzyme defect of mitochondrial fatty acid oxidation. 56
1401059 1992
27
Efficacy of bezafibrate in two patients with mitochondrial trifunctional protein deficiency. 61
32509533 2020
28
Multisystem involvement in Chinese patients with neuromyopathic phenotype of mitochondrial trifunctional protein deficiency. 61
32515919 2020
29
Sensory neuronopathy as a major clinical feature of mitochondrial trifunctional protein deficiency in adults. 61
32253025 2020
30
Novel HADHB mutations in a patient with mitochondrial trifunctional protein deficiency. 61
32257295 2020
31
Identification and functional characterization of mutations within HADHB associated with mitochondrial trifunctional protein deficiency. 61
31521624 2019
32
Evaluation of earlier versus later dietary management in long-chain 3-hydroxyacyl-CoA dehydrogenase or mitochondrial trifunctional protein deficiency: a systematic review. 61
31730477 2019
33
TFPa/HADHA is required for fatty acid beta-oxidation and cardiolipin re-modeling in human cardiomyocytes. 61
31604922 2019
34
RETINAL PHENOTYPE IN A CASE OF LCHAD/TFP DEFICIENCY WITH LATE-STAGE DIAGNOSIS. 61
28301411 2019
35
Management and diagnosis of mitochondrial fatty acid oxidation disorders: focus on very-long-chain acyl-CoA dehydrogenase deficiency. 61
30401918 2019
36
Evaluation of Metabolic Defects in Fatty Acid Oxidation Using Peripheral Blood Mononuclear Cells Loaded with Deuterium-Labeled Fatty Acids. 61
30881520 2019
37
HADHB mutations cause infantile-onset axonal Charcot-Marie-Tooth disease: A report of two cases. 61
29956646 2018
38
Cryo-EM structure of human mitochondrial trifunctional protein. 61
29915090 2018
39
Peripheral Neuropathy, Episodic Rhabdomyolysis, and Hypoparathyroidism in a Patient with Mitochondrial Trifunctional Protein Deficiency. 61
28685493 2018
40
Mitochondrial Trifunctional Protein Deficiency: Severe Cardiomyopathy and Cardiac Transplantation. 61
29124685 2018
41
Clinical and molecular investigation of 14 Japanese patients with complete TFP deficiency: a comparison with Caucasian cases. 61
28515471 2017
42
Pharmacological inhibition of carnitine palmitoyltransferase 1 restores mitochondrial oxidative phosphorylation in human trifunctional protein deficient fibroblasts. 61
28392417 2017
43
Diagnosis of LCHAD/TFP deficiency in an at risk newborn using umbilical cord blood acylcarnitine analysis. 61
27995076 2017
44
Mitochondrial trifunctional protein deficiency: an adult patient with similar progress to Charcot-Marie-Tooth disease. 61
28132977 2017
45
Identification of a Novel HADHB Gene Mutation in an Iranian Patient with Mitochondrial Trifunctional Protein Deficiency. 61
28112527 2017
46
A fetus with mitochondrial trifunctional protein deficiency: Elevation of 3-OH-acylcarnitines in amniotic fluid functionally assured the genetic diagnosis. 61
27014569 2016
47
Mitochondrial trifunctional protein deficiency in human cultured fibroblasts: effects of bezafibrate. 61
26109258 2016
48
Round Table Discussion. 61
27931031 2016
49
Mitochondrial trifunctional protein deficiency due to HADHB gene mutation in a Chinese family. 61
28649548 2015
50
Noncompaction in mitochondrial trifunctional protein deficiency due to a HADHB mutation. 61
26206388 2015

Variations for Mitochondrial Trifunctional Protein Deficiency

ClinVar genetic disease variations for Mitochondrial Trifunctional Protein Deficiency:

6 (show top 50) (show all 213) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 HADHB NM_000183.3(HADHB):c.254+1G>ASNV Pathogenic 431987 rs776172237 2:26492866-26492866 2:26269998-26269998
2 HADHA NM_000182.5(HADHA):c.6_24dup (p.Ile9fs)duplication Pathogenic 579792 rs1456890163 2:26467440-26467441 2:26244572-26244573
3 HADHB NM_000183.3(HADHB):c.685C>T (p.Arg229Ter)SNV Pathogenic 579455 rs759136382 2:26502057-26502057 2:26279189-26279189
4 HADHA NM_000182.5(HADHA):c.612dup (p.Arg205Ter)duplication Pathogenic 638987 2:26453123-26453124 2:26230255-26230256
5 HADHA NM_000182.5(HADHA):c.1644del (p.Arg549fs)deletion Pathogenic 651987 2:26417484-26417484 2:26194615-26194615
6 HADHA NC_000002.11:g.(?_26414109)_(26462021_?)deldeletion Pathogenic 661736 2:26414109-26462021
7 HADHA NM_000182.5(HADHA):c.1689+2T>GSNV Pathogenic 801655 2:26417437-26417437 2:26194568-26194568
8 HADHB NM_000183.3(HADHB):c.1206C>G (p.Tyr402Ter)SNV Pathogenic 801656 2:26507807-26507807 2:26284939-26284939
9 HADHA NC_000002.12:g.(?_26236845)_(26239153_?)deldeletion Pathogenic 831608 2:26459713-26462021
10 HADHA NM_000182.5(HADHA):c.1720_1721del (p.Leu574fs)deletion Pathogenic 845656 2:26416610-26416611 2:26193741-26193742
11 HADHA NM_000182.5(HADHA):c.1690-17_1690-2deldeletion Pathogenic 848128 2:26416643-26416658 2:26193774-26193789
12 HADHA NM_000182.5(HADHA):c.1528G>C (p.Glu510Gln)SNV Pathogenic 100085 rs137852769 2:26418053-26418053 2:26195184-26195184
13 HADHA NM_000182.5(HADHA):c.180+3A>GSNV Pathogenic 8731 rs781222705 2:26461799-26461799 2:26238931-26238931
14 HADHA NM_000182.5(HADHA):c.1678C>T (p.Arg560Ter)SNV Pathogenic 8732 rs137852771 2:26417450-26417450 2:26194581-26194581
15 HADHA NM_000182.5(HADHA):c.2132dup (p.Pro712fs)duplication Pathogenic 8733 2:26414365-26414366 2:26191496-26191497
16 HADHA NM_000182.5(HADHA):c.1025T>C (p.Leu342Pro)SNV Pathogenic 8734 rs137852772 2:26432709-26432709 2:26209840-26209840
17 HADHA NM_000182.5(HADHA):c.845T>A (p.Val282Asp)SNV Pathogenic 8735 rs137852773 2:26437385-26437385 2:26214516-26214516
18 HADHA NM_000182.5(HADHA):c.871C>T (p.Arg291Ter)SNV Pathogenic 8737 rs137852775 2:26437359-26437359 2:26214490-26214490
19 HADHB NM_000183.3(HADHB):c.788A>G (p.Asp263Gly)SNV Pathogenic 14844 rs121913131 2:26502160-26502160 2:26279292-26279292
20 HADHB NM_000183.3(HADHB):c.1331G>A (p.Arg444Lys)SNV Pathogenic 14847 rs121913134 2:26508381-26508381 2:26285513-26285513
21 HADHB HADHB, 1-BP INS, 36-BP DELindel Pathogenic 14848
22 HADHB NM_000183.3(HADHB):c.1364T>G (p.Val455Gly)SNV Pathogenic 14849 rs267606859 2:26508414-26508414 2:26285546-26285546
23 HADHB NM_000183.3(HADHB):c.1175C>T (p.Ala392Val)SNV Pathogenic 190379 rs764623179 2:26507776-26507776 2:26284908-26284908
24 HADHB NM_000183.3(HADHB):c.357dup (p.Ala120fs)duplication Pathogenic 253049 rs886037844 2:26499942-26499943 2:26277074-26277075
25 HADHA NM_000182.5(HADHA):c.1793_1794del (p.His598fs)deletion Pathogenic/Likely pathogenic 188962 rs769580842 2:26416537-26416538 2:26193668-26193669
26 HADHA NM_000182.5(HADHA):c.274_278del (p.Ser92fs)deletion Pathogenic/Likely pathogenic 189105 rs781205883 2:26459759-26459763 2:26236891-26236895
27 HADHA NM_000182.5(HADHA):c.2000+1G>CSNV Pathogenic/Likely pathogenic 554318 rs1167218743 2:26415178-26415178 2:26192309-26192309
28 HADHA NM_000182.5(HADHA):c.1195C>T (p.Arg399Ter)SNV Pathogenic/Likely pathogenic 449455 rs1243779049 2:26426956-26426956 2:26204087-26204087
29 HADHA NM_000182.5(HADHA):c.1086-3_1092deldeletion Pathogenic/Likely pathogenic 370400 rs1057516460 2:26427059-26427068 2:26204190-26204199
30 HADHA NM_000182.5(HADHA):c.453+1G>ASNV Likely pathogenic 370347 rs1057516417 2:26457084-26457084 2:26234216-26234216
31 HADHA NM_000182.5(HADHA):c.574-2A>GSNV Likely pathogenic 835948 2:26453164-26453164 2:26230296-26230296
32 HADHB NM_000183.3(HADHB):c.1375G>A (p.Ala459Thr)SNV Likely pathogenic 801657 2:26508425-26508425 2:26285557-26285557
33 HADHA NM_000182.5(HADHA):c.539C>T (p.Pro180Leu)SNV Likely pathogenic 816540 2:26455062-26455062 2:26232194-26232194
34 HADHB NM_000183.3(HADHB):c.631-2A>CSNV Likely pathogenic 643838 2:26502001-26502001 2:26279133-26279133
35 HADHA NM_000182.5(HADHA):c.1645A>G (p.Arg549Gly)SNV Likely pathogenic 689365 2:26417483-26417483 2:26194614-26194614
36 HADHB NM_000183.3(HADHB):c.209+1G>ASNV Likely pathogenic 225385 rs113112630 2:26486348-26486348 2:26263480-26263480
37 HADHB NM_000183.3(HADHB):c.182G>A (p.Arg61His)SNV Likely pathogenic 14845 rs121913132 2:26486320-26486320 2:26263452-26263452
38 HADHB NM_000183.3(HADHB):c.740G>A (p.Arg247His)SNV Likely pathogenic 14846 rs121913133 2:26502112-26502112 2:26279244-26279244
39 HADHA NM_000182.5(HADHA):c.1132C>T (p.Gln378Ter)SNV Likely pathogenic 8729 rs137852770 2:26427019-26427019 2:26204150-26204150
40 HADHA NM_000182.5(HADHA):c.180+1G>ASNV Likely pathogenic 8730 rs786205088 2:26461801-26461801 2:26238933-26238933
41 HADHB NM_000183.3(HADHB):c.901G>C (p.Gly301Arg)SNV Likely pathogenic 548520 rs891954464 2:26502951-26502951 2:26280083-26280083
42 HADHB NM_000183.3(HADHB):c.255-2A>GSNV Likely pathogenic 844215 2:26496517-26496517 2:26273649-26273649
43 HADHA NM_000182.5(HADHA):c.914T>A (p.Ile305Asn)SNV Conflicting interpretations of pathogenicity 8736 rs137852774 2:26437316-26437316 2:26214447-26214447
44 HADHA NM_000182.5(HADHA):c.-1G>TSNV Conflicting interpretations of pathogenicity 92593 rs72809666 2:26467465-26467465 2:26244597-26244597
45 HADHB NM_000183.3(HADHB):c.246A>G (p.Ala82=)SNV Conflicting interpretations of pathogenicity 92599 rs151302743 2:26492857-26492857 2:26269989-26269989
46 HADHA NM_000182.5(HADHA):c.1947T>A (p.Asn649Lys)SNV Conflicting interpretations of pathogenicity 728421 2:26415232-26415232 2:26192363-26192363
47 HADHB NM_000183.3(HADHB):c.1206C>T (p.Tyr402=)SNV Conflicting interpretations of pathogenicity 703153 2:26507807-26507807 2:26284939-26284939
48 HADHA NM_000182.5(HADHA):c.189A>G (p.Thr63=)SNV Conflicting interpretations of pathogenicity 752873 2:26459848-26459848 2:26236980-26236980
49 HADHA NM_000182.5(HADHA):c.1843A>G (p.Asn615Asp)SNV Conflicting interpretations of pathogenicity 449769 rs61731155 2:26416488-26416488 2:26193619-26193619
50 HADHA NM_000182.5(HADHA):c.2175C>T (p.Gly725=)SNV Conflicting interpretations of pathogenicity 512927 rs375399631 2:26414236-26414236 2:26191367-26191367

UniProtKB/Swiss-Prot genetic disease variations for Mitochondrial Trifunctional Protein Deficiency:

73 (show all 16)
# Symbol AA change Variation ID SNP ID
1 HADHA p.Val282Asp VAR_021125 rs137852773
2 HADHA p.Ile305Asn VAR_021126 rs137852774
3 HADHB p.Arg61His VAR_007493 rs121913132
4 HADHB p.Arg247His VAR_007494 rs121913133
5 HADHB p.Asp263Gly VAR_007495 rs121913131
6 HADHB p.Arg444Lys VAR_017409 rs121913134
7 HADHB p.Gly59Asp VAR_021128
8 HADHB p.Arg61Cys VAR_021129 rs780351691
9 HADHB p.Arg117Gly VAR_021130
10 HADHB p.Leu121Pro VAR_021131 rs773127211
11 HADHB p.Thr133Pro VAR_021132 rs371159065
12 HADHB p.Asp242Gly VAR_021133 rs116612047
13 HADHB p.Gly280Asp VAR_021135 rs751772298
14 HADHB p.Pro294Leu VAR_021136
15 HADHB p.Pro294Arg VAR_021137
16 HADHB p.Gly301Ser VAR_021138 rs891954464

Expression for Mitochondrial Trifunctional Protein Deficiency

Search GEO for disease gene expression data for Mitochondrial Trifunctional Protein Deficiency.

Pathways for Mitochondrial Trifunctional Protein Deficiency

Pathways related to Mitochondrial Trifunctional Protein Deficiency according to KEGG:

36
# Name Kegg Source Accession
1 Fatty acid degradation hsa00071
2 Fatty acid metabolism hsa01212

Pathways related to Mitochondrial Trifunctional Protein Deficiency according to GeneCards Suite gene sharing:

(show all 21)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.93 SLC25A20 LCLAT1 HADHB HADHA HADH ETFDH
2
Show member pathways
12.67 SLC25A20 LCLAT1 HADHB HADHA HADH CPT2
3
Show member pathways
12.36 LCLAT1 HADHB HADHA HADH EHHADH CPT2
4 11.98 HADHB HADHA ACADM
5
Show member pathways
11.92 HADHB HADHA HADH EHHADH ACADS ACADM
6
Show member pathways
11.76 HADHB HADHA HADH
7
Show member pathways
11.72 HADHA HADH EHHADH
8 11.71 HADH EHHADH ACADM
9 11.62 EHHADH CPT2 ACADM
10 11.51 HADHA HADH EHHADH
11
Show member pathways
11.44 HADHB HADH EHHADH
12
Show member pathways
11.38 HADHB HADHA HADH ACADVL ACADS ACADM
13 11.34 HADH ACADVL ACADM
14
Show member pathways
11.31 HADHA HADH EHHADH ACADS
15 11.22 HADHA EHHADH ACADS
16
Show member pathways
11.2 HADHA EHHADH ACADS
17 11.07 EHHADH CPT2 ACADM
18
Show member pathways
11 SLC25A20 HADHB HADHA HADH EHHADH CPT2
19
Show member pathways
10.93 HADHB HADHA EHHADH
20
Show member pathways
10.62 HADHB HADHA HADH ACADM
21 10.61 SLC25A20 CPT2

GO Terms for Mitochondrial Trifunctional Protein Deficiency

Cellular components related to Mitochondrial Trifunctional Protein Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrial matrix GO:0005759 9.73 HADH ETFDH ACADVL ACADS ACADM ACAD10
2 mitochondrial membrane GO:0031966 9.63 HIGD1A ETFDH ACADVL ACADM ACAD9 ACAD11
3 mitochondrial inner membrane GO:0005743 9.61 SLC25A20 HIGD1A HADHB HADHA ETFDH CPT2
4 mitochondrial nucleoid GO:0042645 9.5 HADHB HADHA ACADVL
5 mitochondrion GO:0005739 9.44 SLC25A20 HIGD1A HADHB HADHA HADH ETFDH

Biological processes related to Mitochondrial Trifunctional Protein Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 lipid metabolic process GO:0006629 10.02 LCLAT1 HADHB HADHA HADH EHHADH CPT2
2 oxidation-reduction process GO:0055114 10 HIGD1A HADHA HADH ETFDH EHHADH ACADVL
3 fatty acid metabolic process GO:0006631 9.61 HADHB HADHA HADH EHHADH CPT2 ACADVL
4 fatty acid beta-oxidation using acyl-CoA dehydrogenase GO:0033539 9.55 ETFDH ACADVL ACADS ACADM ACAD11
5 cardiolipin acyl-chain remodeling GO:0035965 9.54 LCLAT1 HADHB HADHA
6 carnitine shuttle GO:0006853 9.43 SLC25A20 CPT2
7 medium-chain fatty acid metabolic process GO:0051791 9.4 ACADM ACAD9
8 fatty acid beta-oxidation GO:0006635 9.32 HADHB HADHA HADH EHHADH CPT2 ACADVL

Molecular functions related to Mitochondrial Trifunctional Protein Deficiency according to GeneCards Suite gene sharing:

(show all 14)
# Name GO ID Score Top Affiliating Genes
1 oxidoreductase activity GO:0016491 9.96 HADHA HADH ETFDH EHHADH ACADVL ACADS
2 transferase activity, transferring acyl groups GO:0016746 9.71 LCLAT1 HADHB CPT2
3 fatty-acyl-CoA binding GO:0000062 9.65 HADHA ACADVL ACAD9
4 enoyl-CoA hydratase activity GO:0004300 9.63 HADHB HADHA EHHADH
5 oxidoreductase activity, acting on the CH-CH group of donors GO:0016627 9.63 ACADVL ACADS ACADM ACAD9 ACAD11 ACAD10
6 3-hydroxyacyl-CoA dehydrogenase activity GO:0003857 9.62 HADHB HADHA HADH EHHADH
7 long-chain-acyl-CoA dehydrogenase activity GO:0004466 9.61 ACADVL ACAD9 ACAD11
8 medium-chain-acyl-CoA dehydrogenase activity GO:0070991 9.58 ACADM ACAD9 ACAD11
9 very-long-chain-acyl-CoA dehydrogenase activity GO:0017099 9.54 ACADVL ACAD9 ACAD11
10 acetyl-CoA C-acyltransferase activity GO:0003988 9.52 HADHB HADHA
11 long-chain-enoyl-CoA hydratase activity GO:0016508 9.51 HADHA EHHADH
12 flavin adenine dinucleotide binding GO:0050660 9.5 ETFDH ACADVL ACADS ACADM ACAD9 ACAD11
13 long-chain-3-hydroxyacyl-CoA dehydrogenase activity GO:0016509 9.49 HADHA EHHADH
14 acyl-CoA dehydrogenase activity GO:0003995 9.1 ACADVL ACADS ACADM ACAD9 ACAD11 ACAD10

Sources for Mitochondrial Trifunctional Protein Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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