MCID: SNG007
MIFTS: 35

Sengers Syndrome

Categories: Genetic diseases, Rare diseases, Metabolic diseases, Cardiovascular diseases

Aliases & Classifications for Sengers Syndrome

MalaCards integrated aliases for Sengers Syndrome:

Name: Sengers Syndrome 54 12 50 24 71 13 52 14
Mitochondrial Dna Depletion Syndrome 10 12 24 71
Cardiomyopathy and Cataract 50 24 71
Cataract and Cardiomyopathy 50 29 69
Mtdps10 24 71
Cardiomyopathic Mitochondrial Dna Depletion Syndrome 10 50

Characteristics:

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
variable severity
high risk of death in infancy due to cardiac failure


HPO:

32
sengers syndrome:
Onset and clinical course variable expressivity infantile onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Sengers Syndrome

NIH Rare Diseases : 50 the following summary is from orphanet, a european reference portal for information on rare diseases and orphan drugs.orpha number: 1369disease definitioncongenitalcataract - hypertrophic cardiomyopathy - mitochrondrial myopathy (ccm) is a mitochondrial disease (see this term) characterized by cataracts, hypertrophic cardiomyopathy, muscle weakness and lactic acidosis after exercise.epidemiologyprevalence of ccm is unknown; approximately 40 cases have been reported to date in disparate locations throughout the world.clinical descriptionclinical features include congenital cataract (total or rapidly progressive), hypertrophic cardiomyopathy, muscle weakness and lactic acidosis after exercise. ccm may present in two forms, a neonatal lethal form or a chronic form. hypertrophic cardiomyopathy is diagnosed at birth in half of the patients in both forms. approximately half of the patients die within the first year of life due to cardiac failure. nystagmus, strabismus, hypotonia, hyporeflexia and delayed motor development are occasional features. marked lactic acidemia occurs with even limited muscular exertion. patients who survive neonatal period and infancy, manifest the chronic form with stable cardiomyopathy and myopathy and have a normal intellect. physical mobility is impaired due to muscular weakness in most patients.etiologyin the majority of ccm patients mutations (nonsense, frame-shift, start codon or splice site) in the agk gene have been identified. the agk gene encodes the mitochondrial acylglycerol kinase which plays a role in the assembly of adeninenucleotide translocator (ant), an essential component of the oxidative phosphorylation in mitochondria. two patients with distinct autosomal recessiveslc25a4 mutations have been reported (one of whom had cardiomyopathy but not cataract). the slc25a4 gene encodes the heart and muscle specific isoform 1 of the mitochondrial ant. the etiology remains genetically unsolved in the rest of cases of ccm. the milder affected individuals carried either splice site or start codon mutations.diagnostic methodsdiagnostic procedures include serum and urine analysis for lactic acid, radiology and echocardiogram for findings of cardiomyopathy. muscle biopsy from cardiac and skeletal muscle reveals storage of lipid and glycogen, mitochondrial abnormalities, ant deficiency and mild decrease of respiratory chain complexes i and iv. genetic testing may reveal autosomal recessive mutations in agk and slc25a4 and it should be considered early in diagnostic workup.differential diagnosisdifferential diagnoses include mitochondrial encephalo-cardio-myopathy due to tmem70 deficiency, isolated atp synthase deficiency and barth syndrome (see these terms).antenatal diagnosisprenatal genetic testing may be possible for families with affected children.genetic counselingthe reported mutations are transmitted in an autosomal recessive manner.management and treatmentccm patients require cataract surgery during infancy and medical management of cardiomyopathy with standard therapy. patients may require palliative care and a wheelchair for locomotion.prognosisapproximately half of the reported patients die in the first year of life due to cardiac failure. the longest surviving patients are in their fifth decade of life.visit the orphanet disease page for more resources. last updated: 6/3/2014

MalaCards based summary : Sengers Syndrome, also known as mitochondrial dna depletion syndrome 10, is related to myopathy, myofibrillar, 2 and congenital cataract-hypertrophic cardiomyopathy-mitochondrial myopathy syndrome, and has symptoms including congenital cataract, nystagmus and strabismus. An important gene associated with Sengers Syndrome is AGK (Acylglycerol Kinase). Affiliated tissues include skeletal muscle, testes and heart, and related phenotype is Increased shRNA abundance (Z-score > 2).

UniProtKB/Swiss-Prot : 71 Mitochondrial DNA depletion syndrome 10: An autosomal recessive mitochondrial disorder characterized by congenital cataracts, hypertrophic cardiomyopathy, skeletal myopathy, exercise intolerance, and lactic acidosis. Mental development is normal, but affected individuals may die early from cardiomyopathy.

OMIM : 54
Sengers syndrome is an autosomal recessive mitochondrial disorder characterized by congenital cataracts, hypertrophic cardiomyopathy, skeletal myopathy, exercise intolerance, and lactic acidosis. Mental development is normal, but affected individuals may die early from cardiomyopathy (summary by Mayr et al., 2012). Skeletal muscle biopsies of 2 affected individuals showed severe mtDNA depletion (Calvo et al., 2012). (212350)

Related Diseases for Sengers Syndrome

Diseases related to Sengers Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

id Related Disease Score Top Affiliating Genes
1 myopathy, myofibrillar, 2 10.9
2 congenital cataract-hypertrophic cardiomyopathy-mitochondrial myopathy syndrome 10.8
3 cardiomyopathy 9.9
4 cataract 9.6
5 cutis laxa 9.6
6 frontal encephalocele 9.6 AGK SLC25A4
7 protoplasmic astrocytoma 9.2 AGK SERAC1 SLC25A4
8 cataract 38, autosomal recessive 7.8 ABHD12 AGK PTDSS1 SERAC1 SLC25A4

Graphical network of the top 20 diseases related to Sengers Syndrome:



Diseases related to Sengers Syndrome

Symptoms & Phenotypes for Sengers Syndrome

Symptoms via clinical synopsis from OMIM:

54

Neurologic- Central Nervous System:
hypotonia
delayed motor development
normal cognition

Head And Neck- Eyes:
strabismus
myopia
glaucoma
cataracts, infantile

Cardiovascular- Heart:
hypertrophic cardiomyopathy

Respiratory:
respiratory insufficiency

Laboratory- Abnormalities:
increased serum lactate, particularly after exercise
intermittent 3-methylglutaconic aciduria

Muscle Soft Tissue:
hypotonia
fatigue
muscle weakness
exercise intolerance
lipid storage myopathy
more
Growth- Other:
poor growth

Metabolic Features:
lactic acidosis

Hematology:
thrombocytopenia (1 patient)


Clinical features from OMIM:

212350

Human phenotypes related to Sengers Syndrome:

32 (show all 20)
id Description HPO Frequency HPO Source Accession
1 congenital cataract 32 HP:0000519
2 nystagmus 32 HP:0000639
3 strabismus 32 HP:0000486
4 myopia 32 HP:0000545
5 thrombocytopenia 32 occasional (7.5%) HP:0001873
6 glaucoma 32 HP:0000501
7 fatigue 32 HP:0012378
8 hypertrophic cardiomyopathy 32 HP:0001639
9 muscle weakness 32 HP:0001324
10 exercise intolerance 32 HP:0003546
11 increased serum lactate 32 HP:0002151
12 myopathy 32 HP:0003198
13 motor delay 32 HP:0001270
14 easy fatigability 32 HP:0003388
15 respiratory insufficiency 32 HP:0002093
16 muscular hypotonia 32 HP:0001252
17 mitochondrial myopathy 32 HP:0003737
18 3-methylglutaconic aciduria 32 HP:0003535
19 growth delay 32 HP:0001510
20 exercise-induced lactic acidemia 32 HP:0004901

UMLS symptoms related to Sengers Syndrome:


fatigue, muscle weakness

GenomeRNAi Phenotypes related to Sengers Syndrome according to GeneCards Suite gene sharing:

26
id Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-100 9.55 PTDSS1
2 Increased shRNA abundance (Z-score > 2) GR00366-A-108 9.55 SLC25A4
3 Increased shRNA abundance (Z-score > 2) GR00366-A-133 9.55 PTDSS1
4 Increased shRNA abundance (Z-score > 2) GR00366-A-16 9.55 PTDSS1
5 Increased shRNA abundance (Z-score > 2) GR00366-A-164 9.55 PTDSS1
6 Increased shRNA abundance (Z-score > 2) GR00366-A-166 9.55 SLC25A4
7 Increased shRNA abundance (Z-score > 2) GR00366-A-169 9.55 PTDSS1
8 Increased shRNA abundance (Z-score > 2) GR00366-A-192 9.55 PTDSS1
9 Increased shRNA abundance (Z-score > 2) GR00366-A-194 9.55 PTDSS1 SLC25A4
10 Increased shRNA abundance (Z-score > 2) GR00366-A-214 9.55 SLC25A4
11 Increased shRNA abundance (Z-score > 2) GR00366-A-4 9.55 PTDSS1
12 Increased shRNA abundance (Z-score > 2) GR00366-A-43 9.55 SLC25A4
13 Increased shRNA abundance (Z-score > 2) GR00366-A-63 9.55 SLC25A4
14 Increased shRNA abundance (Z-score > 2) GR00366-A-7 9.55 PTDSS1
15 Increased shRNA abundance (Z-score > 2) GR00366-A-73 9.55 SLC25A4
16 Increased shRNA abundance (Z-score > 2) GR00366-A-93 9.55 SLC25A4

Drugs & Therapeutics for Sengers Syndrome

Search Clinical Trials , NIH Clinical Center for Sengers Syndrome

Genetic Tests for Sengers Syndrome

Genetic tests related to Sengers Syndrome:

id Genetic test Affiliating Genes
1 Cataract and Cardiomyopathy 29
2 Sengers Syndrome 24 AGK

Anatomical Context for Sengers Syndrome

MalaCards organs/tissues related to Sengers Syndrome:

39
Skeletal Muscle, Testes, Heart

Publications for Sengers Syndrome

Articles related to Sengers Syndrome:

id Title Authors Year
1
Sengers Syndrome-Associated Mitochondrial Acylglycerol Kinase Is a Subunit of the Human TIM22 Protein Import Complex. ( 28712726 )
2017
2
Mutation in the AGK gene in two siblings with unusual Sengers syndrome. ( 28868593 )
2017
3
Acylglycerol Kinase Mutated in Sengers Syndrome Is a Subunit of the TIM22 Protein Translocase in Mitochondria. ( 28712724 )
2017
4
Sengers syndrome: a unique cause of severe hypertrophic cardiomyopathy. ( 26231691 )
2015
5
Sengers syndrome: six novel AGK mutations in seven new families and review of the phenotypic and mutational spectrum of 29 patients. ( 25208612 )
2014
6
Mitochondrial citrate synthase crystals: novel finding in Sengers syndrome caused by acylglycerol kinase (AGK) mutations. ( 23266196 )
2013
7
Lack of the mitochondrial protein acylglycerol kinase causes Sengers syndrome. ( 22284826 )
2012
8
Neuroradiologic findings in Sengers syndrome. ( 18639755 )
2008
9
Adenine nucleotide translocator 1 deficiency associated with Sengers syndrome. ( 12112053 )
2002
10
Cardiac transplantation for hypertrophic cardiomyopathy associated with Sengers syndrome. ( 8526648 )
1995

Variations for Sengers Syndrome

ClinVar genetic disease variations for Sengers Syndrome:

6 (show all 11)
id Gene Variation Type Significance SNP ID Assembly Location
1 AGK AGK, IVS3DS, T-C, +2 single nucleotide variant Pathogenic
2 AGK AGK, TYR390TER undetermined variant Pathogenic
3 AGK AGK, IVS13DS, G-T, +1 single nucleotide variant Pathogenic
4 AGK AGK, MET1ILE undetermined variant Pathogenic
5 AGK NM_018238.3(AGK): c.517C> T (p.Gln173Ter) single nucleotide variant Pathogenic rs387907024 GRCh37 Chromosome 7, 141315364: 141315364
6 AGK AGK, TYR102TER undetermined variant Pathogenic
7 AGK NM_018238.3(AGK): c.841C> T (p.Arg281Ter) single nucleotide variant Pathogenic rs387907025 GRCh37 Chromosome 7, 141341162: 141341162
8 AGK AGK, TYR224TER undetermined variant Pathogenic
9 AGK AGK, IVS16DS, G-A, +5 single nucleotide variant Pathogenic
10 AGK NM_018238.3(AGK): c.409C> T (p.Arg137Ter) single nucleotide variant Pathogenic rs746709222 GRCh37 Chromosome 7, 141313964: 141313964
11 AGK NM_018238.3(AGK): c.424-3C> G single nucleotide variant Pathogenic rs766413410 GRCh37 Chromosome 7, 141315268: 141315268

Expression for Sengers Syndrome

Search GEO for disease gene expression data for Sengers Syndrome.

Pathways for Sengers Syndrome

GO Terms for Sengers Syndrome

Biological processes related to Sengers Syndrome according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 phospholipid biosynthetic process GO:0008654 8.62 PTDSS1 SERAC1

Sources for Sengers Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 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 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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