DLDD
MCID: DHY010
MIFTS: 48

Dihydrolipoamide Dehydrogenase Deficiency (DLDD)

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

Aliases & Classifications for Dihydrolipoamide Dehydrogenase Deficiency

MalaCards integrated aliases for Dihydrolipoamide Dehydrogenase Deficiency:

Name: Dihydrolipoamide Dehydrogenase Deficiency 57 25 20 43 58 72 36 13 39
Dld Deficiency 57 25 20 43 58 72
E3 Deficiency 57 25 20 43 72
Maple Syrup Urine Disease, Type Iii 57 20 43
Lactic Acidosis Due to Lipoamide Dehydrogenase Deficiency 43 72
E3-Deficient Maple Syrup Urine Disease 20 58
Pyruvate Dehydrogenase E3 Deficiency 20 58
Lipoamide Dehydrogenase Deficiency 43 29
Maple Syrup Urine Disease, Type 3 29 6
Dldd 57 72
Lactic Acidosis, Congenital Infantile, Due to Lad Deficiency 70
Lipoamide Dehydrogenase Deficiency, Lactic Acidosis Due to 57
Nadh Cytochrome B5 Reductase Deficiency 70
Dihydrolipoyl Dehydrogenase Deficiency 43
Lactic Acidosis Due to Lad Deficiency 43
Maple Syrup Urine Disease Type Iii 72
Msud Type Iii 72
Msud Type 3 6

Characteristics:

Orphanet epidemiological data:

58
pyruvate dehydrogenase e3 deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood; Age of death: adolescent,late childhood;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
highly variable severity
onset usually in the neonatal period although later onset has been reported
some patients may have normal psychomotor development
high mortality in infancy and early childhood (in some patients)


HPO:

31
dihydrolipoamide dehydrogenase deficiency:
Inheritance autosomal recessive inheritance
Onset and clinical course variable expressivity


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


Summaries for Dihydrolipoamide Dehydrogenase Deficiency

MedlinePlus Genetics : 43 Dihydrolipoamide dehydrogenase deficiency is a severe condition that can affect several body systems. Signs and symptoms of this condition usually appear shortly after birth, and they can vary widely among affected individuals.A common feature of dihydrolipoamide dehydrogenase deficiency is a potentially life-threatening buildup of lactic acid in tissues (lactic acidosis), which can cause nausea, vomiting, severe breathing problems, and an abnormal heartbeat. Neurological problems are also common in this condition; the first symptoms in affected infants are often decreased muscle tone (hypotonia) and extreme tiredness (lethargy). As the problems worsen, affected infants can have difficulty feeding, decreased alertness, and seizures. Liver problems can also occur in dihydrolipoamide dehydrogenase deficiency, ranging from an enlarged liver (hepatomegaly) to life-threatening liver failure. In some affected people, liver disease, which can begin anytime from infancy to adulthood, is the primary symptom. The liver problems are usually associated with recurrent vomiting and abdominal pain. Rarely, people with dihydrolipoamide dehydrogenase deficiency experience weakness of the muscles used for movement (skeletal muscles), particularly during exercise; droopy eyelids; or a weakened heart muscle (cardiomyopathy). Other features of this condition include excess ammonia in the blood (hyperammonemia), a buildup of molecules called ketones in the body (ketoacidosis), or low blood sugar levels (hypoglycemia).Typically, the signs and symptoms of dihydrolipoamide dehydrogenase deficiency occur in episodes that may be triggered by fever, injury, or other stresses on the body. Affected individuals are usually symptom-free between episodes. Many infants with this condition do not survive the first few years of life because of the severity of these episodes. Affected individuals who survive past early childhood often have delayed growth and neurological problems, including intellectual disability, muscle stiffness (spasticity), difficulty coordinating movements (ataxia), and seizures.

MalaCards based summary : Dihydrolipoamide Dehydrogenase Deficiency, also known as dld deficiency, is related to maple syrup urine disease and pyruvate dehydrogenase e3-binding protein deficiency, and has symptoms including seizures, ataxia and headache. An important gene associated with Dihydrolipoamide Dehydrogenase Deficiency is DLD (Dihydrolipoamide Dehydrogenase), and among its related pathways/superpathways are Glycolysis / Gluconeogenesis and Citrate cycle (TCA cycle). Affiliated tissues include liver, and related phenotypes are vomiting and neurodevelopmental delay

GARD : 20 Dihydrolipoamide dehydrogenase (DLD) deficiency is a very rare condition that can vary in age of onset, symptoms and severity. The condition may be characterized by early-onset lactic acidosis and delayed development (most commonly); later-onset neurological dysfunction; or adult-onset isolated liver disease. Signs and symptoms may include lactic acidosis shortly after birth; hypotonia and lethargy in infancy; feeding difficulties; seizures ; and various other health issues. Liver problems can range from hepatomegaly to life-threatening liver failure. Symptoms often occur in episodes that may be triggered by illness or other stresses on the body. Many affected infants do not survive the first few years of life; those who survive through early childhood often have growth delay and intellectual disability. Some with onset later in childhood may have neurological dysfunction with normal cognitive development. DLD deficiency is caused by mutations in the DLD gene and is inherited in an autosomal recessive manner.

OMIM® : 57 DLD deficiency is an autosomal recessive metabolic disorder characterized biochemically by a combined deficiency of the branched-chain alpha-keto acid dehydrogenase complex (BCKDC), pyruvate dehydrogenase complex (PDC), and alpha-ketoglutarate dehydrogenase complex (KGDC). This is the result of E3 being a common component of all 3 mitochondrial multienzyme complexes. Clinically, affected individuals have lactic acidosis and neurologic deterioration due to sensitivity of the central nervous system to defects in oxidative metabolism. E3 deficiency is often associated with increased urinary excretion of alpha-keto acids, such as pyruvate (summary by Hong et al., 1996). E3 deficiency can also be associated with increased concentrations of branched-chain amino acids, as observed in maple syrup urine disease (MSUD; 248600), and is sometimes referred to as 'MSUD type III,' although patients with E3 deficiency have additional biochemical defects (Chuang and Shih, 2001; Robinson, 2001). (246900) (Updated 05-Apr-2021)

KEGG : 36 Dihydrolipoamide dehydrogenase (DLD) deficiency, also known as maple syrup urine disease type III, is a rare autosomal recessive disorder. DLD functions as the E3 subunit of three mitochondrial enzyme complexes: branched chain alpha-ketoacid dehydrogenase, alpha-ketoglutarate dehydrogenase, and pyruvate dehydrogenase. DLD deficiency variably presents with either a severe neonatal encephalopathic phenotype or a primarily hepatic phenotype.

UniProtKB/Swiss-Prot : 72 Dihydrolipoamide dehydrogenase deficiency: An autosomal recessive metabolic disorder characterized biochemically by a combined deficiency of the branched-chain alpha-keto acid dehydrogenase complex (BCKDC), pyruvate dehydrogenase complex (PDC), and alpha-ketoglutarate dehydrogenase complex (KGDC). Clinically, affected individuals have lactic acidosis and neurologic deterioration due to sensitivity of the central nervous system to defects in oxidative metabolism.

Wikipedia : 73 Dihydrolipoamide dehydrogenase (DLD), also known as dihydrolipoyl dehydrogenase, mitochondrial, is an... more...

GeneReviews: NBK220444

Related Diseases for Dihydrolipoamide Dehydrogenase Deficiency

Diseases related to Dihydrolipoamide Dehydrogenase Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 41)
# Related Disease Score Top Affiliating Genes
1 maple syrup urine disease 31.3 DLD BCKDHB
2 pyruvate dehydrogenase e3-binding protein deficiency 11.1
3 pyruvate dehydrogenase e1-alpha deficiency 10.5
4 lactic acidosis 10.3
5 liver disease 10.3
6 citrullinemia, classic 10.2
7 metabolic acidosis 10.2
8 myopathy 10.2
9 hypotonia 10.2
10 friedreich ataxia 10.1
11 3-methylglutaconic aciduria, type iii 10.0
12 alacrima, achalasia, and mental retardation syndrome 10.0
13 carbonic anhydrase va deficiency, hyperammonemia due to 10.0
14 organic acidemia 10.0
15 myoglobinuria 10.0
16 microcephaly 10.0
17 peripheral nervous system disease 10.0
18 mitochondrial myopathy 10.0
19 neuropathy 10.0
20 spasticity 10.0
21 acute liver failure 10.0
22 ifap syndrome 2 9.9
23 ptosis 9.9
24 hypertrophic cardiomyopathy 9.9
25 pfeiffer syndrome 9.8
26 hypercholesterolemia, familial, 1 9.8
27 hypertriglyceridemia, familial 9.8
28 leigh syndrome 9.8
29 xanthomatosis 9.8
30 familial hypercholesterolemia 9.8
31 renovascular hypertension 9.8
32 learning disability 9.8
33 mitochondrial dna-associated leigh syndrome and narp 9.8
34 mitochondrial disorders 9.8
35 nuclear gene-encoded leigh syndrome spectrum 9.8
36 encephalopathy 9.8
37 homozygous familial hypercholesterolemia 9.8
38 branched-chain keto acid dehydrogenase kinase deficiency 9.8 DLD BCKDHB
39 congenital methemoglobinemia 9.7 CYB5R3 ATP5MGL
40 glycine encephalopathy 9.7 DLD BCKDHB
41 methemoglobinemia due to deficiency of methemoglobin reductase 9.6 CYB5R3 ATP5MGL

Graphical network of the top 20 diseases related to Dihydrolipoamide Dehydrogenase Deficiency:



Diseases related to Dihydrolipoamide Dehydrogenase Deficiency

Symptoms & Phenotypes for Dihydrolipoamide Dehydrogenase Deficiency

Human phenotypes related to Dihydrolipoamide Dehydrogenase Deficiency:

58 31 (show all 35)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 vomiting 58 31 hallmark (90%) Very frequent (99-80%) HP:0002013
2 neurodevelopmental delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0012758
3 increased serum lactate 58 31 hallmark (90%) Very frequent (99-80%) HP:0002151
4 lactic acidosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0003128
5 generalized hypotonia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001290
6 global developmental delay 31 hallmark (90%) HP:0001263
7 spasticity 58 31 frequent (33%) Frequent (79-30%) HP:0001257
8 hepatomegaly 58 31 occasional (7.5%) Frequent (79-30%) HP:0002240
9 hypoglycemia 58 31 frequent (33%) Frequent (79-30%) HP:0001943
10 elevated hepatic transaminase 58 31 occasional (7.5%) Frequent (79-30%) HP:0002910
11 lethargy 58 31 frequent (33%) Frequent (79-30%) HP:0001254
12 feeding difficulties 58 31 frequent (33%) Frequent (79-30%) HP:0011968
13 elevated plasma branched chain amino acids 58 31 frequent (33%) Frequent (79-30%) HP:0008344
14 hypercoagulability 58 31 frequent (33%) Frequent (79-30%) HP:0100724
15 hepatic encephalopathy 58 31 frequent (33%) Frequent (79-30%) HP:0002480
16 increased urine alpha-ketoglutarate concentration 58 31 frequent (33%) Frequent (79-30%) HP:0012402
17 seizure 31 frequent (33%) HP:0001250
18 failure to thrive 58 31 occasional (7.5%) Occasional (29-5%) HP:0001508
19 ataxia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001251
20 behavioral abnormality 58 31 occasional (7.5%) Occasional (29-5%) HP:0000708
21 microcephaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0000252
22 reduced visual acuity 58 31 occasional (7.5%) Occasional (29-5%) HP:0007663
23 hepatic failure 58 31 occasional (7.5%) Occasional (29-5%) HP:0001399
24 hyperammonemia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001987
25 cardiomyopathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0001638
26 muscle spasm 58 31 occasional (7.5%) Occasional (29-5%) HP:0003394
27 abnormal cardiac ventricular function 58 31 occasional (7.5%) Occasional (29-5%) HP:0030872
28 decreased plasma carnitine 58 31 occasional (7.5%) Occasional (29-5%) HP:0003234
29 hyperisoleucinemia 58 31 occasional (7.5%) Occasional (29-5%) HP:0010913
30 decreased liver function 31 occasional (7.5%) HP:0001410
31 seizures 58 Frequent (79-30%)
32 hypertrophic cardiomyopathy 31 HP:0001639
33 dystonia 31 HP:0001332
34 encephalopathy 31 HP:0001298
35 metabolic acidosis 31 HP:0001942

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
seizures
ataxia
dystonia
lethargy
hypotonia
more
Laboratory Abnormalities:
hypoglycemia
elevated pyruvate (in most patients)
elevated branched-chain amino acids (in most patients)
elevated alpha-ketoglutarate (in most patients)
decreased activities of the pyruvate dehydrogenase complex, the alpha-ketoglutarate dehydrogenase complex, and the branched-chain alpha-keto acid dehydrogenase complex
more
Metabolic Features:
lactic acidosis
metabolic acidosis
episodic decompensation

Abdomen Liver:
hepatomegaly (in some patients)
liver dysfunction (in some patients)

Head And Neck Head:
microcephaly

Cardiovascular Heart:
hypertrophic cardiomyopathy

Abdomen Gastrointestinal:
poor feeding
vomiting, recurrent, severe

Clinical features from OMIM®:

246900 (Updated 05-Apr-2021)

UMLS symptoms related to Dihydrolipoamide Dehydrogenase Deficiency:


seizures; ataxia; headache; lethargy; cyanosis; dyspnea on exertion

GenomeRNAi Phenotypes related to Dihydrolipoamide Dehydrogenase Deficiency according to GeneCards Suite gene sharing:

26 (show all 21)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-105 9.7 CYB5R3
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-170 9.7 DLD
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-195 9.7 CYB5R3
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-24 9.7 DLD
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-35 9.7 DLD
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-42 9.7 DLD
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-43 9.7 CYB5R3
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-50 9.7 CYB5R3
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-51 9.7 DLD
10 Decreased shRNA abundance (Z-score < -2) GR00366-A-77 9.7 DLD
11 Decreased shRNA abundance (Z-score < -2) GR00366-A-85 9.7 CYB5R3
12 Increased shRNA abundance (Z-score > 2) GR00366-A-158 9.36 DLD
13 Increased shRNA abundance (Z-score > 2) GR00366-A-180 9.36 DLD
14 Increased shRNA abundance (Z-score > 2) GR00366-A-192 9.36 CYB5R3
15 Increased shRNA abundance (Z-score > 2) GR00366-A-203 9.36 DLD
16 Increased shRNA abundance (Z-score > 2) GR00366-A-24 9.36 CYB5R3
17 Increased shRNA abundance (Z-score > 2) GR00366-A-68 9.36 CYB5R3
18 Increased shRNA abundance (Z-score > 2) GR00366-A-69 9.36 DLD
19 Increased shRNA abundance (Z-score > 2) GR00366-A-74 9.36 CYB5R3
20 Increased shRNA abundance (Z-score > 2) GR00366-A-78 9.36 CYB5R3 DLD
21 Increased shRNA abundance (Z-score > 2) GR00366-A-82 9.36 CYB5R3

Drugs & Therapeutics for Dihydrolipoamide Dehydrogenase Deficiency

Search Clinical Trials , NIH Clinical Center for Dihydrolipoamide Dehydrogenase Deficiency

Genetic Tests for Dihydrolipoamide Dehydrogenase Deficiency

Genetic tests related to Dihydrolipoamide Dehydrogenase Deficiency:

# Genetic test Affiliating Genes
1 Maple Syrup Urine Disease, Type 3 29 DLD
2 Lipoamide Dehydrogenase Deficiency 29

Anatomical Context for Dihydrolipoamide Dehydrogenase Deficiency

MalaCards organs/tissues related to Dihydrolipoamide Dehydrogenase Deficiency:

40
Liver

Publications for Dihydrolipoamide Dehydrogenase Deficiency

Articles related to Dihydrolipoamide Dehydrogenase Deficiency:

(show top 50) (show all 85)
# Title Authors PMID Year
1
Molecular basis of lipoamide dehydrogenase deficiency in Ashkenazi Jews. 6 57 25
9934985 1999
2
Novel mutations in dihydrolipoamide dehydrogenase deficiency in two cousins with borderline-normal PDH complex activity. 61 57 6
16770810 2006
3
Identification of two mutations in a compound heterozygous child with dihydrolipoamide dehydrogenase deficiency. 61 57 6
8968745 1996
4
Riboflavin responsive mitochondrial myopathy is a new phenotype of dihydrolipoamide dehydrogenase deficiency. The chaperon-like effect of vitamin B2. 61 25 6
25251739 2014
5
Elevated plasma citrulline: look for dihydrolipoamide dehydrogenase deficiency. 6 25 61
23995961 2014
6
Newborn screening for dihydrolipoamide dehydrogenase deficiency: Citrulline as a useful analyte. 61 6 25
27896107 2014
7
Dihydrolipoamide dehydrogenase deficiency: a still overlooked cause of recurrent acute liver failure and Reye-like syndrome. 6 25 61
23478190 2013
8
Leigh syndrome in a girl with a novel DLD mutation causing E3 deficiency. 61 6 25
23290025 2013
9
A novel mutation in the dihydrolipoamide dehydrogenase E3 subunit gene (DLD) resulting in an atypical form of alpha-ketoglutarate dehydrogenase deficiency. 6 57
15712224 2005
10
Identification of a common mutation (Gly194Cys) in both Arab Moslem and Ashkenazi Jewish patients with dihydrolipoamide dehydrogenase (E3) deficiency: possible beneficial effect of vitamin therapy. 57 6
14765544 2003
11
Novel mutations in a boy with dihydrolipoamide dehydrogenase deficiency. 61 25 6
11687750 2001
12
Lipoamide dehydrogenase deficiency due to a novel mutation in the interface domain. 57 6
10448086 1999
13
Leigh disease with deficiency of lipoamide dehydrogenase: treatment failure with dichloroacetate. 57 6
8652022 1996
14
Identification of two missense mutations in a dihydrolipoamide dehydrogenase-deficient patient. 57 6
8506365 1993
15
Alpha-ketoglutarate dehydrogenase deficiency presenting as congenital lactic acidosis. 6 57
1640293 1992
16
Dihydrolipoyl dehydrogenase deficiency: a therapeutic trial with branched-chain amino acid restriction. 6 57
3769994 1986
17
Mutations in the dimer interface of dihydrolipoamide dehydrogenase promote site-specific oxidative damages in yeast and human cells. 6 25
21930696 2011
18
Deficiency of dihydrolipoamide dehydrogenase due to two mutant alleles (E340K and G101del). Analysis of a family and prenatal testing. 6 25
9540846 1997
19
Stimulation of reactive oxygen species generation by disease-causing mutations of lipoamide dehydrogenase. 6 61
21558426 2011
20
Cryptic proteolytic activity of dihydrolipoamide dehydrogenase. 61 6
17404228 2007
21
Fourteen new mutations of BCKDHA, BCKDHB and DBT genes associated with maple syrup urine disease (MSUD) in Malaysian population. 6
30228974 2018
22
Clinical characteristics and mutation analysis of five Chinese patients with maple syrup urine disease. 6
29307017 2018
23
MRI and clinical features of maple syrup urine disease: preliminary results in 10 cases. 6
28830848 2017
24
Twenty novel mutations in BCKDHA, BCKDHB and DBT genes in a cohort of 52 Saudi Arabian patients with maple syrup urine disease. 6
28417071 2017
25
Enzymopenic Congenital Methemoglobinemia in Children of the Republic of Sakha (Yakutia). 6
27879543 2017
26
Structural alterations induced by ten disease-causing mutations of human dihydrolipoamide dehydrogenase analyzed by hydrogen/deuterium-exchange mass spectrometry: Implications for the structural basis of E3 deficiency. 6
27544700 2016
27
Difficulties in recognition of pyruvate dehydrogenase complex deficiency on the basis of clinical and biochemical features. The role of next-generation sequencing. 6
27144126 2016
28
New perspective in diagnostics of mitochondrial disorders: two years' experience with whole-exome sequencing at a national paediatric centre. 6
27290639 2016
29
Evolution of maple syrup urine disease in patients diagnosed by newborn screening versus late diagnosis. 6
26232051 2015
30
Phenylbutyrate increases pyruvate dehydrogenase complex activity in cells harboring a variety of defects. 6
25356417 2014
31
Validation for clinical use of, and initial clinical experience with, a novel approach to population-based carrier screening using high-throughput, next-generation DNA sequencing. 6
24374108 2014
32
Mutation Spectrum and Birth Prevalence of Inborn Errors of Metabolism among Emiratis: A study from Tawam Hospital Metabolic Center, United Arab Emirates. 6
24516753 2014
33
Identification of three novel mutations by studying the molecular genetics of Maple Syrup Urine Disease (MSUD) in the Lebanese population. 6
27896100 2014
34
Mutations in human lipoyltransferase gene LIPT1 cause a Leigh disease with secondary deficiency for pyruvate and alpha-ketoglutarate dehydrogenase. 25 61
24341803 2013
35
Analysis of gene mutations among South Indian patients with maple syrup urine disease: identification of four novel mutations. 6
24772966 2013
36
[Population frequency and age of c.806C > T mutation in CYB5R3 gene as cause of recessive congenital methemoglobinemia in Yakutia]. 6
23866629 2013
37
Molecular genetic analysis of MSUD from India reveals mutations causing altered protein truncation affecting the C-termini of E1α and E1β. 6
22593002 2012
38
Analysis of gene mutations in Chinese patients with maple syrup urine disease. 6
22727569 2012
39
Dihydrolipoamide dehydrogenase (DLD) deficiency in a Spanish patient with myopathic presentation due to a new mutation in the interface domain. 61 25
20652410 2010
40
Maple syrup urine disease: further evidence that newborn screening may fail to identify variant forms. 6
20307994 2010
41
Targeted comparative genomic hybridization array for the detection of single- and multiexon gene deletions and duplications. 6
19282776 2009
42
Molecular genetics of maple syrup urine disease in the Turkish population. 6
19480318 2009
43
[Hereditary diseases among Yakuts]. 6
19062529 2008
44
Molecular and structural analyses of maple syrup urine disease and identification of a founder mutation in a Portuguese Gypsy community. 6
18378174 2008
45
TAT-mediated delivery of LAD restores pyruvate dehydrogenase complex activity in the mitochondria of patients with LAD deficiency. 6
18362926 2008
46
Description of the mutations in 15 subjects with variant forms of maple syrup urine disease. 6
17922217 2007
47
Mutational spectrum of maple syrup urine disease in Spain. 6
16786533 2006
48
Structural insight into interactions between dihydrolipoamide dehydrogenase (E3) and E3 binding protein of human pyruvate dehydrogenase complex. 6
16442803 2006
49
Biochemical and molecular diagnosis of lipoamide dehydrogenase deficiency in a North American Ashkenazi Jewish family. 6
16601893 2006
50
Identification of twelve novel mutations in patients with classic and variant forms of maple syrup urine disease. 6
14517957 2003

Variations for Dihydrolipoamide Dehydrogenase Deficiency

ClinVar genetic disease variations for Dihydrolipoamide Dehydrogenase Deficiency:

6 (show top 50) (show all 195)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 DLD NM_000108.5(DLD):c.214A>G (p.Lys72Glu) SNV Pathogenic 11964 rs121964987 GRCh37: 7:107542785-107542785
GRCh38: 7:107902340-107902340
2 DLD NM_000108.5(DLD):c.1463C>T (p.Pro488Leu) SNV Pathogenic 11965 rs121964988 GRCh37: 7:107559543-107559543
GRCh38: 7:107919098-107919098
3 DLD NM_000108.5(DLD):c.1483A>G (p.Arg495Gly) SNV Pathogenic 11968 rs121964989 GRCh37: 7:107559657-107559657
GRCh38: 7:107919212-107919212
4 DLD NM_000108.5(DLD):c.1178T>C (p.Ile393Thr) SNV Pathogenic 11969 rs121964991 GRCh37: 7:107557849-107557849
GRCh38: 7:107917404-107917404
5 DLD NM_000108.5(DLD):c.1081A>G (p.Met361Val) SNV Pathogenic 11972 rs121964993 GRCh37: 7:107557752-107557752
GRCh38: 7:107917307-107917307
6 DLD NM_000108.5(DLD):c.1444A>G (p.Arg482Gly) SNV Pathogenic 40187 rs397514650 GRCh37: 7:107559524-107559524
GRCh38: 7:107919079-107919079
7 DLD NM_000108.5(DLD):c.140T>C (p.Ile47Thr) SNV Pathogenic 40188 rs397514651 GRCh37: 7:107542204-107542204
GRCh38: 7:107901759-107901759
8 CYB5R3 NM_000398.7(CYB5R3):c.464-2A>C SNV Pathogenic 245 rs794728013 GRCh37: 22:43023696-43023696
GRCh38: 22:42627690-42627690
9 CYB5R3 NM_000398.7(CYB5R3):c.226+2T>C SNV Pathogenic 801428 rs1601938489 GRCh37: 22:43027382-43027382
GRCh38: 22:42631376-42631376
10 DLD NM_000108.5(DLD):c.105del (p.Thr34_Tyr35insTer) Deletion Pathogenic 553084 rs1554396895 GRCh37: 7:107533710-107533710
GRCh38: 7:107893265-107893265
11 DLD NM_000108.5(DLD):c.12G>A (p.Trp4Ter) SNV Pathogenic 572549 rs1562908173 GRCh37: 7:107531707-107531707
GRCh38: 7:107891262-107891262
12 DLD NC_000007.14:g.(?_107901728)_(107906378_?)del Deletion Pathogenic 831013 GRCh37: 7:107542173-107546823
GRCh38:
13 DLD NM_000108.5(DLD):c.946C>T (p.Arg316Ter) SNV Pathogenic 854640 GRCh37: 7:107557309-107557309
GRCh38: 7:107916864-107916864
14 DLD NM_000108.5(DLD):c.1340_1343CAGA[1] (p.Asp448fs) Microsatellite Pathogenic 856335 GRCh37: 7:107558470-107558473
GRCh38: 7:107918025-107918028
15 DLD NM_000108.5(DLD):c.821dup (p.Leu274fs) Duplication Pathogenic 960146 GRCh37: 7:107556085-107556086
GRCh38: 7:107915640-107915641
16 DLD NM_000108.5(DLD):c.308_310delinsT (p.Gly103fs) Indel Pathogenic 969750 GRCh37: 7:107543963-107543965
GRCh38: 7:107903518-107903520
17 BCKDHB NM_183050.4(BCKDHB):c.487G>T (p.Glu163Ter) SNV Pathogenic 370827 rs1057516799 GRCh37: 6:80878601-80878601
GRCh38: 6:80168884-80168884
18 BCKDHB NM_183050.4(BCKDHB):c.331C>T (p.Arg111Ter) SNV Pathogenic 928847 GRCh37: 6:80838934-80838934
GRCh38: 6:80129217-80129217
19 BCKDHB NM_183050.4(BCKDHB):c.82_92GGCGCGGGGCT[3] (p.Phe35fs) Microsatellite Pathogenic 189101 rs398124601 GRCh37: 6:80816489-80816490
GRCh38: 6:80106772-80106773
20 DLD NM_000108.5(DLD):c.685G>T (p.Gly229Cys) SNV Pathogenic 11966 rs121964990 GRCh37: 7:107555951-107555951
GRCh38: 7:107915506-107915506
21 DLD NM_000108.5(DLD):c.104dup (p.Tyr35Ter) Duplication Pathogenic 370072 rs753234219 GRCh37: 7:107533708-107533709
GRCh38: 7:107893263-107893264
22 BCKDHB NM_183050.4(BCKDHB):c.752T>C (p.Val251Ala) SNV Pathogenic 96608 rs398124593 GRCh37: 6:80910660-80910660
GRCh38: 6:80200943-80200943
23 BCKDHB NM_183050.4(BCKDHB):c.970C>T (p.Arg324Ter) SNV Pathogenic 96621 rs398124603 GRCh37: 6:80982870-80982870
GRCh38: 6:80273153-80273153
24 BCKDHB NM_183050.4(BCKDHB):c.593_594AG[1] (p.Ser199_Pro200insTer) Microsatellite Pathogenic 96599 rs398124587 GRCh37: 6:80878707-80878708
GRCh38: 6:80168990-80168991
25 BCKDHB NM_183050.4(BCKDHB):c.82_92GGCGCGGGGCT[1] (p.Ala32fs) Microsatellite Pathogenic 96618 rs398124601 GRCh37: 6:80816490-80816500
GRCh38: 6:80106773-80106783
26 BCKDHB NM_183050.4(BCKDHB):c.832G>A (p.Gly278Ser) SNV Pathogenic 65771 rs386834233 GRCh37: 6:80910740-80910740
GRCh38: 6:80201023-80201023
27 BCKDHB NM_183050.4(BCKDHB):c.548G>C (p.Arg183Pro) SNV Pathogenic 11937 rs79761867 GRCh37: 6:80878662-80878662
GRCh38: 6:80168945-80168945
28 BCKDHB NM_183050.4(BCKDHB):c.853C>T (p.Arg285Ter) SNV Pathogenic 96615 rs398124598 GRCh37: 6:80912831-80912831
GRCh38: 6:80203114-80203114
29 ATP5MGL , CYB5R3 NM_000398.7(CYB5R3):c.22-3269dup Duplication Pathogenic 1033008 GRCh37: 22:43036114-43036115
GRCh38: 22:42640108-42640109
30 CYB5R3 NM_000398.7(CYB5R3):c.226G>A (p.Gly76Ser) SNV Pathogenic 1033009 GRCh37: 22:43027384-43027384
GRCh38: 22:42631378-42631378
31 DLD NM_000108.5(DLD):c.1416_1422del (p.Tyr473fs) Deletion Pathogenic/Likely pathogenic 840283 GRCh37: 7:107559492-107559498
GRCh38: 7:107919047-107919053
32 DLD NM_000108.5(DLD):c.1123G>A (p.Glu375Lys) SNV Pathogenic/Likely pathogenic 11971 rs121964992 GRCh37: 7:107557794-107557794
GRCh38: 7:107917349-107917349
33 DLD NM_000108.5(DLD):c.875+1G>A SNV Pathogenic/Likely pathogenic 11970 rs1328820332 GRCh37: 7:107556142-107556142
GRCh38: 7:107915697-107915697
34 DLD NM_000108.5(DLD):c.112C>T (p.Gln38Ter) SNV Pathogenic/Likely pathogenic 370700 rs1057516698 GRCh37: 7:107533717-107533717
GRCh38: 7:107893272-107893272
35 DLD NM_000108.5(DLD):c.633dup (p.Val212fs) Duplication Pathogenic/Likely pathogenic 371111 rs1040811473 GRCh37: 7:107546755-107546756
GRCh38: 7:107906310-107906311
36 DLD NM_000108.5(DLD):c.345del (p.Val116fs) Deletion Likely pathogenic 550203 rs1554398625 GRCh37: 7:107545409-107545409
GRCh38: 7:107904964-107904964
37 CYB5R3 NM_000398.7(CYB5R3):c.806C>T (p.Pro269Leu) SNV Likely pathogenic 989273 GRCh37: 22:43015879-43015879
GRCh38: 22:42619873-42619873
38 DLD NM_000108.5(DLD):c.1444_1445AG[1] (p.Arg482fs) Microsatellite Likely pathogenic 551065 rs1554400713 GRCh37: 7:107559524-107559525
GRCh38: 7:107919079-107919080
39 DLD NM_000108.5(DLD):c.338-2_338-1delinsT Indel Likely pathogenic 551198 rs1554398624 GRCh37: 7:107545401-107545402
GRCh38: 7:107904956-107904957
40 DLD NM_000108.5(DLD):c.199-1G>A SNV Likely pathogenic 552664 rs1554398264 GRCh37: 7:107542769-107542769
GRCh38: 7:107902324-107902324
41 DLD NM_000108.5(DLD):c.82del (p.Ser28fs) Deletion Likely pathogenic 371579 rs764704217 GRCh37: 7:107533685-107533685
GRCh38: 7:107893240-107893240
42 DLD NM_000108.5(DLD):c.223dup (p.Thr75fs) Duplication Likely pathogenic 371362 rs1057517214 GRCh37: 7:107542791-107542792
GRCh38: 7:107902346-107902347
43 DLD NM_000108.5(DLD):c.1516_1519TCAA[1] (p.Ile507fs) Microsatellite Likely pathogenic 371542 rs777884525 GRCh37: 7:107559688-107559691
GRCh38: 7:107919243-107919246
44 DLD NM_000108.5(DLD):c.39+1G>A SNV Likely pathogenic 371615 rs111257462 GRCh37: 7:107531735-107531735
GRCh38: 7:107891290-107891290
45 DLD NM_000108.5(DLD):c.1436A>T (p.Asp479Val) SNV Likely pathogenic 40186 rs397514649 GRCh37: 7:107559516-107559516
GRCh38: 7:107919071-107919071
46 DLD NM_000108.5(DLD):c.1236+1G>T SNV Likely pathogenic 553091 rs1554400483 GRCh37: 7:107557908-107557908
GRCh38: 7:107917463-107917463
47 DLD NM_000108.5(DLD):c.1429_1432del (p.Cys477fs) Deletion Likely pathogenic 554494 rs1554400704 GRCh37: 7:107559509-107559512
GRCh38: 7:107919064-107919067
48 DLD NM_000108.5(DLD):c.1421del (p.Gly474fs) Deletion Likely pathogenic 555593 rs1554400699 GRCh37: 7:107559500-107559500
GRCh38: 7:107919055-107919055
49 DLD NM_000108.5(DLD):c.268-2A>G SNV Likely pathogenic 556197 rs1554398461 GRCh37: 7:107543921-107543921
GRCh38: 7:107903476-107903476
50 DLD NM_000108.5(DLD):c.198+1G>A SNV Likely pathogenic 556283 rs1554398193 GRCh37: 7:107542263-107542263
GRCh38: 7:107901818-107901818

UniProtKB/Swiss-Prot genetic disease variations for Dihydrolipoamide Dehydrogenase Deficiency:

72
# Symbol AA change Variation ID SNP ID
1 DLD p.Lys72Glu VAR_006907 rs121964987
2 DLD p.Pro488Leu VAR_006908 rs121964988
3 DLD p.Gly229Cys VAR_015820 rs121964990
4 DLD p.Arg495Gly VAR_015821 rs121964989
5 DLD p.Ile47Thr VAR_076985 rs397514651
6 DLD p.Met361Val VAR_076987 rs121964993
7 DLD p.Glu375Lys VAR_076988 rs121964992
8 DLD p.Ile393Thr VAR_076989 rs121964991
9 DLD p.Asp479Val VAR_076990 rs397514649
10 DLD p.Arg482Gly VAR_076991 rs397514650

Expression for Dihydrolipoamide Dehydrogenase Deficiency

Search GEO for disease gene expression data for Dihydrolipoamide Dehydrogenase Deficiency.

Pathways for Dihydrolipoamide Dehydrogenase Deficiency

Pathways related to Dihydrolipoamide Dehydrogenase Deficiency according to KEGG:

36
# Name Kegg Source Accession
1 Glycolysis / Gluconeogenesis hsa00010
2 Citrate cycle (TCA cycle) hsa00020
3 Valine, leucine and isoleucine degradation hsa00280
4 Pyruvate metabolism hsa00620

GO Terms for Dihydrolipoamide Dehydrogenase Deficiency

Cellular components related to Dihydrolipoamide Dehydrogenase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrial matrix GO:0005759 8.96 DLD BCKDHB
2 mitochondrion GO:0005739 8.92 DLD CYB5R3 BCKDHB ATP5MGL

Biological processes related to Dihydrolipoamide Dehydrogenase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 oxidation-reduction process GO:0055114 9.13 DLD CYB5R3 BCKDHB
2 branched-chain amino acid catabolic process GO:0009083 8.62 DLD BCKDHB

Molecular functions related to Dihydrolipoamide Dehydrogenase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 oxidoreductase activity GO:0016491 9.33 DLD CYB5R3 BCKDHB
2 flavin adenine dinucleotide binding GO:0050660 8.96 DLD CYB5R3
3 NAD binding GO:0051287 8.62 DLD CYB5R3

Sources for Dihydrolipoamide Dehydrogenase Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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