MCID: DHY010
MIFTS: 34

Dihydrolipoamide Dehydrogenase Deficiency

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

Aliases & Classifications for Dihydrolipoamide Dehydrogenase Deficiency

MalaCards integrated aliases for Dihydrolipoamide Dehydrogenase Deficiency:

Name: Dihydrolipoamide Dehydrogenase Deficiency 57 24 53 25 59 75 37 13 40
Dld Deficiency 57 24 53 25 59 75
E3 Deficiency 57 24 53 25 75
Maple Syrup Urine Disease, Type Iii 57 53 25
Lactic Acidosis Due to Lipoamide Dehydrogenase Deficiency 25 75
E3-Deficient Maple Syrup Urine Disease 53 59
Pyruvate Dehydrogenase E3 Deficiency 53 59
Lipoamide Dehydrogenase Deficiency 24 25
Maple Syrup Urine Disease, Type 3 29 6
Dldd 57 75
Lactic Acidosis, Congenital Infantile, Due to Lad Deficiency 73
Lipoamide Dehydrogenase Deficiency, Lactic Acidosis Due to 57
Nadh Cytochrome B5 Reductase Deficiency 73
Dihydrolipoyl Dehydrogenase Deficiency 25
Lactic Acidosis Due to Lad Deficiency 25
Maple Syrup Urine Disease Type Iii 75
Msud Type Iii 75

Characteristics:

Orphanet epidemiological data:

59
pyruvate dehydrogenase e3 deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood; Age of death: adolescent,late childhood;

OMIM:

57
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:

32
dihydrolipoamide dehydrogenase deficiency:
Onset and clinical course variable expressivity
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Dihydrolipoamide Dehydrogenase Deficiency

NIH Rare Diseases : 53 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.

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 ataxia, cyanosis 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 generalized hypotonia and vomiting

Genetics Home Reference : 25 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.

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)

UniProtKB/Swiss-Prot : 75 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 : 76 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:

# Related Disease Score Top Affiliating Genes
1 maple syrup urine disease 11.2
2 pyruvate dehydrogenase e3-binding protein deficiency 11.0
3 mitochondrial myopathy 9.9
4 infantile liver failure syndrome 1 9.9
5 acute liver failure 9.9
6 myopathy 9.9
7 hypercholesterolemia, familial 9.6
8 homozygous familial hypercholesterolemia 9.6

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



Diseases related to Dihydrolipoamide Dehydrogenase Deficiency

Symptoms & Phenotypes for Dihydrolipoamide Dehydrogenase Deficiency

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
seizures
ataxia
dystonia
lethargy
hypotonia
more
Cardiovascular Heart:
hypertrophic cardiomyopathy

Metabolic Features:
lactic acidosis
metabolic acidosis
episodic decompensation

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

Head And Neck Head:
microcephaly

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
Abdomen Gastrointestinal:
poor feeding
vomiting, recurrent, severe


Clinical features from OMIM:

246900

Human phenotypes related to Dihydrolipoamide Dehydrogenase Deficiency:

59 32 (show all 34)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 generalized hypotonia 59 32 hallmark (90%) Very frequent (99-80%) HP:0001290
2 vomiting 59 32 hallmark (90%) Very frequent (99-80%) HP:0002013
3 increased serum lactate 59 32 hallmark (90%) Very frequent (99-80%) HP:0002151
4 lactic acidosis 59 32 hallmark (90%) Very frequent (99-80%) HP:0003128
5 neurodevelopmental delay 59 32 hallmark (90%) Very frequent (99-80%) HP:0012758
6 seizures 59 32 frequent (33%) Frequent (79-30%) HP:0001250
7 lethargy 59 32 frequent (33%) Frequent (79-30%) HP:0001254
8 spasticity 59 32 frequent (33%) Frequent (79-30%) HP:0001257
9 hypoglycemia 59 32 frequent (33%) Frequent (79-30%) HP:0001943
10 hepatomegaly 59 32 occasional (7.5%) Frequent (79-30%) HP:0002240
11 hepatic encephalopathy 59 32 frequent (33%) Frequent (79-30%) HP:0002480
12 elevated hepatic transaminases 59 32 occasional (7.5%) Frequent (79-30%) HP:0002910
13 elevated plasma branched chain amino acids 59 32 frequent (33%) Frequent (79-30%) HP:0008344
14 feeding difficulties 59 32 frequent (33%) Frequent (79-30%) HP:0011968
15 increased urine alpha-ketoglutarate concentration 59 32 frequent (33%) Frequent (79-30%) HP:0012402
16 hypercoagulability 59 32 frequent (33%) Frequent (79-30%) HP:0100724
17 microcephaly 59 32 occasional (7.5%) Occasional (29-5%) HP:0000252
18 behavioral abnormality 59 32 occasional (7.5%) Occasional (29-5%) HP:0000708
19 ataxia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001251
20 hepatic failure 59 32 occasional (7.5%) Occasional (29-5%) HP:0001399
21 failure to thrive 59 32 occasional (7.5%) Occasional (29-5%) HP:0001508
22 cardiomyopathy 59 32 occasional (7.5%) Occasional (29-5%) HP:0001638
23 hyperammonemia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001987
24 decreased plasma carnitine 59 32 occasional (7.5%) Occasional (29-5%) HP:0003234
25 muscle cramps 59 32 occasional (7.5%) Occasional (29-5%) HP:0003394
26 reduced visual acuity 59 32 occasional (7.5%) Occasional (29-5%) HP:0007663
27 hyperisoleucinemia 59 32 occasional (7.5%) Occasional (29-5%) HP:0010913
28 abnormal cardiac ventricular function 59 32 occasional (7.5%) Occasional (29-5%) HP:0030872
29 global developmental delay 32 hallmark (90%) HP:0001263
30 encephalopathy 32 HP:0001298
31 dystonia 32 HP:0001332
32 decreased liver function 32 occasional (7.5%) HP:0001410
33 hypertrophic cardiomyopathy 32 HP:0001639
34 metabolic acidosis 32 HP:0001942

UMLS symptoms related to Dihydrolipoamide Dehydrogenase Deficiency:


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

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

Anatomical Context for Dihydrolipoamide Dehydrogenase Deficiency

MalaCards organs/tissues related to Dihydrolipoamide Dehydrogenase Deficiency:

41
Liver

Publications for Dihydrolipoamide Dehydrogenase Deficiency

Articles related to Dihydrolipoamide Dehydrogenase Deficiency:

# Title Authors Year
1
Riboflavin responsive mitochondrial myopathy is a new phenotype of dihydrolipoamide dehydrogenase deficiency. The chaperon-like effect of vitamin B2. ( 25251739 )
2014
2
Newborn screening for dihydrolipoamide dehydrogenase deficiency: Citrulline as a useful analyte. ( 27896107 )
2014
3
Elevated plasma citrulline: look for dihydrolipoamide dehydrogenase deficiency. ( 23995961 )
2013
4
Dihydrolipoamide dehydrogenase deficiency: a still overlooked cause of recurrent acute liver failure and Reye-like syndrome. ( 23478190 )
2013
5
Novel mutations in dihydrolipoamide dehydrogenase deficiency in two cousins with borderline-normal PDH complex activity. ( 16770810 )
2006
6
Novel mutations in a boy with dihydrolipoamide dehydrogenase deficiency. ( 11687750 )
2001
7
Identification of two mutations in a compound heterozygous child with dihydrolipoamide dehydrogenase deficiency. ( 8968745 )
1996
8
Identification of two missense mutations in a dihydrolipoamide dehydrogenase-deficient patient. ( 8506365 )
1993
9
Dihydrolipoamide Dehydrogenase Deficiency ( 25032271 )
1993

Variations for Dihydrolipoamide Dehydrogenase Deficiency

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

75
# 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

ClinVar genetic disease variations for Dihydrolipoamide Dehydrogenase Deficiency:

6
(show all 38)
# Gene Variation Type Significance SNP ID Assembly Location
1 DLD NM_000108.4(DLD): c.214A> G (p.Lys72Glu) single nucleotide variant Pathogenic rs121964987 GRCh37 Chromosome 7, 107542785: 107542785
2 DLD NM_000108.4(DLD): c.214A> G (p.Lys72Glu) single nucleotide variant Pathogenic rs121964987 GRCh38 Chromosome 7, 107902340: 107902340
3 DLD NM_000108.4(DLD): c.1463C> T (p.Pro488Leu) single nucleotide variant Pathogenic rs121964988 GRCh37 Chromosome 7, 107559543: 107559543
4 DLD NM_000108.4(DLD): c.1463C> T (p.Pro488Leu) single nucleotide variant Pathogenic rs121964988 GRCh38 Chromosome 7, 107919098: 107919098
5 DLD NM_000108.4(DLD): c.685G> T (p.Gly229Cys) single nucleotide variant Pathogenic rs121964990 GRCh37 Chromosome 7, 107555951: 107555951
6 DLD NM_000108.4(DLD): c.685G> T (p.Gly229Cys) single nucleotide variant Pathogenic rs121964990 GRCh38 Chromosome 7, 107915506: 107915506
7 DLD DLD, 1-BP INS, 105A insertion Pathogenic
8 DLD NM_000108.4(DLD): c.1483A> G (p.Arg495Gly) single nucleotide variant Pathogenic rs121964989 GRCh37 Chromosome 7, 107559657: 107559657
9 DLD NM_000108.4(DLD): c.1483A> G (p.Arg495Gly) single nucleotide variant Pathogenic rs121964989 GRCh38 Chromosome 7, 107919212: 107919212
10 DLD NM_000108.4(DLD): c.1178T> C (p.Ile393Thr) single nucleotide variant Pathogenic rs121964991 GRCh37 Chromosome 7, 107557849: 107557849
11 DLD NM_000108.4(DLD): c.1178T> C (p.Ile393Thr) single nucleotide variant Pathogenic rs121964991 GRCh38 Chromosome 7, 107917404: 107917404
12 DLD DLD, IVS9DS, G-A, +1 single nucleotide variant Pathogenic
13 DLD NM_000108.4(DLD): c.1123G> A (p.Glu375Lys) single nucleotide variant Pathogenic/Likely pathogenic rs121964992 GRCh37 Chromosome 7, 107557794: 107557794
14 DLD NM_000108.4(DLD): c.1123G> A (p.Glu375Lys) single nucleotide variant Pathogenic/Likely pathogenic rs121964992 GRCh38 Chromosome 7, 107917349: 107917349
15 DLD NM_000108.4(DLD): c.1081A> G (p.Met361Val) single nucleotide variant Pathogenic rs121964993 GRCh37 Chromosome 7, 107557752: 107557752
16 DLD NM_000108.4(DLD): c.1081A> G (p.Met361Val) single nucleotide variant Pathogenic rs121964993 GRCh38 Chromosome 7, 107917307: 107917307
17 DLD NM_000108.4(DLD): c.1436A> T (p.Asp479Val) single nucleotide variant Pathogenic rs397514649 GRCh37 Chromosome 7, 107559516: 107559516
18 DLD NM_000108.4(DLD): c.1436A> T (p.Asp479Val) single nucleotide variant Pathogenic rs397514649 GRCh38 Chromosome 7, 107919071: 107919071
19 DLD NM_000108.4(DLD): c.1444A> G (p.Arg482Gly) single nucleotide variant Pathogenic rs397514650 GRCh37 Chromosome 7, 107559524: 107559524
20 DLD NM_000108.4(DLD): c.1444A> G (p.Arg482Gly) single nucleotide variant Pathogenic rs397514650 GRCh38 Chromosome 7, 107919079: 107919079
21 DLD NM_000108.4(DLD): c.140T> C (p.Ile47Thr) single nucleotide variant Pathogenic rs397514651 GRCh37 Chromosome 7, 107542204: 107542204
22 DLD NM_000108.4(DLD): c.140T> C (p.Ile47Thr) single nucleotide variant Pathogenic rs397514651 GRCh38 Chromosome 7, 107901759: 107901759
23 DLD NM_000108.4(DLD): c.788G> A (p.Arg263His) single nucleotide variant Uncertain significance rs145670503 GRCh37 Chromosome 7, 107556054: 107556054
24 DLD NM_000108.4(DLD): c.788G> A (p.Arg263His) single nucleotide variant Uncertain significance rs145670503 GRCh38 Chromosome 7, 107915609: 107915609
25 DLD NM_000108.4(DLD): c.39+1G> A single nucleotide variant Likely pathogenic rs111257462 GRCh38 Chromosome 7, 107891290: 107891290
26 DLD NM_000108.4(DLD): c.39+1G> A single nucleotide variant Likely pathogenic rs111257462 GRCh37 Chromosome 7, 107531735: 107531735
27 DLD NM_000108.4(DLD): c.82delT (p.Ser28Leufs) deletion Likely pathogenic rs1057517380 GRCh38 Chromosome 7, 107893242: 107893242
28 DLD NM_000108.4(DLD): c.82delT (p.Ser28Leufs) deletion Likely pathogenic rs1057517380 GRCh37 Chromosome 7, 107533687: 107533687
29 DLD NM_000108.4(DLD): c.104dupA (p.Tyr35Terfs) duplication Likely pathogenic rs1057516213 GRCh37 Chromosome 7, 107533709: 107533709
30 DLD NM_000108.4(DLD): c.104dupA (p.Tyr35Terfs) duplication Likely pathogenic rs1057516213 GRCh38 Chromosome 7, 107893264: 107893264
31 DLD NM_000108.4(DLD): c.112C> T (p.Gln38Ter) single nucleotide variant Likely pathogenic rs1057516698 GRCh37 Chromosome 7, 107533717: 107533717
32 DLD NM_000108.4(DLD): c.112C> T (p.Gln38Ter) single nucleotide variant Likely pathogenic rs1057516698 GRCh38 Chromosome 7, 107893272: 107893272
33 DLD NM_000108.4(DLD): c.223dupA (p.Thr75Asnfs) duplication Likely pathogenic rs1057517214 GRCh37 Chromosome 7, 107542794: 107542794
34 DLD NM_000108.4(DLD): c.223dupA (p.Thr75Asnfs) duplication Likely pathogenic rs1057517214 GRCh38 Chromosome 7, 107902349: 107902349
35 DLD NM_000108.4(DLD): c.633dupA (p.Val212Serfs) duplication Likely pathogenic rs1057517016 GRCh37 Chromosome 7, 107546762: 107546762
36 DLD NM_000108.4(DLD): c.633dupA (p.Val212Serfs) duplication Likely pathogenic rs1057517016 GRCh38 Chromosome 7, 107906317: 107906317
37 DLD NM_000108.4(DLD): c.1520_1523delTCAA (p.Ile507Thrfs) deletion Likely pathogenic rs1057517354 GRCh37 Chromosome 7, 107559694: 107559697
38 DLD NM_000108.4(DLD): c.1520_1523delTCAA (p.Ile507Thrfs) deletion Likely pathogenic rs1057517354 GRCh38 Chromosome 7, 107919249: 107919252

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:

37
# Name Kegg Source Accession
1 Glycolysis / Gluconeogenesis hsa00010
2 Citrate cycle (TCA cycle) hsa00020
3 Pyruvate metabolism hsa00620

GO Terms for Dihydrolipoamide Dehydrogenase Deficiency

Sources for Dihydrolipoamide Dehydrogenase Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
Content
Loading form....