MCID: SNG007
MIFTS: 33

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 57 12 53 75 13 55 15
Cataract and Cardiomyopathy 53 29 6 73
Mitochondrial Dna Depletion Syndrome 10 57 12 75
Cardiomyopathy and Cataract 57 53 75
Mtdps10 57 75
Cardiomyopathic Mitochondrial Dna Depletion Syndrome 10 53
Mitochondrial Dna Depletion Syndrome 10 ; Mtdps10 57
Senger Syndrome ) 40

Characteristics:

OMIM:

57
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 : 53 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.

MalaCards based summary : Sengers Syndrome, also known as cataract and cardiomyopathy, is related to congenital cataract-hypertrophic cardiomyopathy-mitochondrial myopathy syndrome and cataract, and has symptoms including fatigue and muscle weakness. An important gene associated with Sengers Syndrome is AGK (Acylglycerol Kinase). Affiliated tissues include skeletal muscle, heart and testes, and related phenotypes are nystagmus and muscular hypotonia

OMIM : 57 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)

UniProtKB/Swiss-Prot : 75 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.

Wikipedia : 76 Sengers syndrome is a rare autosomal recessive condition characterised by congenital cataract,... more...

Related Diseases for Sengers Syndrome

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

# Related Disease Score Top Affiliating Genes
1 congenital cataract-hypertrophic cardiomyopathy-mitochondrial myopathy syndrome 31.5 AGK SLC25A4
2 cataract 28.1 ABHD12 AGK
3 encephalopathy, axonal, with necrotizing myopathy, cardiomyopathy, and cataracts 12.0
4 myopathy, myofibrillar, 2 11.0
5 hypertrophic cardiomyopathy 10.0
6 lactic acidosis 9.8
7 cutis laxa 9.7

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:

57
Muscle Soft Tissue:
muscle weakness
fatigue
exercise intolerance
hypotonia
lipid storage myopathy
more
Cardiovascular Heart:
hypertrophic cardiomyopathy

Metabolic Features:
lactic acidosis

Growth Other:
poor growth

Hematology:
thrombocytopenia (1 patient)

Respiratory:
respiratory insufficiency

Head And Neck Eyes:
strabismus
myopia
glaucoma
cataracts, infantile

Neurologic Central Nervous System:
hypotonia
delayed motor development
normal cognition

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


Clinical features from OMIM:

212350

Human phenotypes related to Sengers Syndrome:

32 (show all 21)
# Description HPO Frequency HPO Source Accession
1 nystagmus 32 HP:0000639
2 muscular hypotonia 32 HP:0001252
3 muscle weakness 32 HP:0001324
4 respiratory insufficiency 32 HP:0002093
5 myopathy 32 HP:0003198
6 fatigue 32 HP:0012378
7 hypertrophic cardiomyopathy 32 HP:0001639
8 strabismus 32 HP:0000486
9 growth delay 32 HP:0001510
10 myopia 32 HP:0000545
11 thrombocytopenia 32 occasional (7.5%) HP:0001873
12 increased serum lactate 32 HP:0002151
13 mitochondrial myopathy 32 HP:0003737
14 glaucoma 32 HP:0000501
15 motor delay 32 HP:0001270
16 exercise intolerance 32 HP:0003546
17 generalized hypotonia 32 HP:0001290
18 congenital cataract 32 HP:0000519
19 easy fatigability 32 HP:0003388
20 3-methylglutaconic aciduria 32 HP:0003535
21 exercise-induced lactic acidemia 32 HP:0004901

UMLS symptoms related to Sengers Syndrome:


fatigue, muscle weakness

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:

# Genetic test Affiliating Genes
1 Cataract and Cardiomyopathy 29 AGK

Anatomical Context for Sengers Syndrome

MalaCards organs/tissues related to Sengers Syndrome:

41
Skeletal Muscle, Heart, Testes, Liver

Publications for Sengers Syndrome

Articles related to Sengers Syndrome:

(show all 13)
# Title Authors Year
1
Extending the phenotypic spectrum of Sengers syndrome: Congenital lactic acidosis with synthetic liver dysfunction. ( 29682452 )
2018
2
Sustained intraoperative bradycardia revealing Sengers syndrome. ( 29416160 )
2018
3
Sengers Syndrome-Associated Mitochondrial Acylglycerol Kinase Is a Subunit of the Human TIM22 Protein Import Complex. ( 28712726 )
2017
4
Acylglycerol Kinase Mutated in Sengers Syndrome Is a Subunit of the TIM22 Protein Translocase in Mitochondria. ( 28712724 )
2017
5
Sustained intraoperative bradycardia revealing Sengers syndrome. ( 29217863 )
2017
6
Mutation in the AGK gene in two siblings with unusual Sengers syndrome. ( 28868593 )
2017
7
Sengers syndrome: a unique cause of severe hypertrophic cardiomyopathy. ( 26231691 )
2015
8
Sengers syndrome: six novel AGK mutations in seven new families and review of the phenotypic and mutational spectrum of 29 patients. ( 25208612 )
2014
9
Mitochondrial citrate synthase crystals: novel finding in Sengers syndrome caused by acylglycerol kinase (AGK) mutations. ( 23266196 )
2013
10
Lack of the mitochondrial protein acylglycerol kinase causes Sengers syndrome. ( 22284826 )
2012
11
Neuroradiologic findings in Sengers syndrome. ( 18639755 )
2008
12
Adenine nucleotide translocator 1 deficiency associated with Sengers syndrome. ( 12112053 )
2002
13
Cardiac transplantation for hypertrophic cardiomyopathy associated with Sengers syndrome. ( 8526648 )
1995

Variations for Sengers Syndrome

ClinVar genetic disease variations for Sengers Syndrome:

6
(show top 50) (show all 113)
# Gene Variation Type Significance SNP ID Assembly Location
1 AGK NM_018238.3(AGK): c.141+2T> C single nucleotide variant Pathogenic GRCh38 Chromosome 7, 141593187: 141593187
2 AGK NM_018238.3(AGK): c.141+2T> C single nucleotide variant Pathogenic GRCh37 Chromosome 7, 141292987: 141292987
3 AGK NM_018238.3(AGK): c.1170T> G (p.Tyr390Ter) single nucleotide variant Pathogenic GRCh37 Chromosome 7, 141352625: 141352625
4 AGK NM_018238.3(AGK): c.1170T> G (p.Tyr390Ter) single nucleotide variant Pathogenic GRCh38 Chromosome 7, 141652825: 141652825
5 AGK NM_018238.3(AGK): c.975+1G> T single nucleotide variant Pathogenic rs868431923 GRCh38 Chromosome 7, 141641909: 141641909
6 AGK NM_018238.3(AGK): c.975+1G> T single nucleotide variant Pathogenic rs868431923 GRCh37 Chromosome 7, 141341709: 141341709
7 AGK NM_018238.3(AGK): c.517C> T (p.Gln173Ter) single nucleotide variant Pathogenic rs387907024 GRCh37 Chromosome 7, 141315364: 141315364
8 AGK NM_018238.3(AGK): c.517C> T (p.Gln173Ter) single nucleotide variant Pathogenic rs387907024 GRCh38 Chromosome 7, 141615564: 141615564
9 AGK NM_018238.3(AGK): c.306T> G (p.Tyr102Ter) single nucleotide variant Pathogenic GRCh38 Chromosome 7, 141611203: 141611203
10 AGK NM_018238.3(AGK): c.306T> G (p.Tyr102Ter) single nucleotide variant Pathogenic GRCh37 Chromosome 7, 141311003: 141311003
11 AGK NM_018238.3(AGK): c.841C> T (p.Arg281Ter) single nucleotide variant Pathogenic rs387907025 GRCh37 Chromosome 7, 141341162: 141341162
12 AGK NM_018238.3(AGK): c.841C> T (p.Arg281Ter) single nucleotide variant Pathogenic rs387907025 GRCh38 Chromosome 7, 141641362: 141641362
13 AGK NM_018238.3(AGK): c.672C> G (p.Tyr224Ter) single nucleotide variant Pathogenic rs771945804 GRCh38 Chromosome 7, 141636963: 141636963
14 AGK NM_018238.3(AGK): c.672C> G (p.Tyr224Ter) single nucleotide variant Pathogenic rs771945804 GRCh37 Chromosome 7, 141336763: 141336763
15 AGK AGK, IVS16DS, G-A, +5 single nucleotide variant Pathogenic
16 AGK NM_018238.3(AGK): c.409C> T (p.Arg137Ter) single nucleotide variant Pathogenic rs746709222 GRCh37 Chromosome 7, 141313964: 141313964
17 AGK NM_018238.3(AGK): c.409C> T (p.Arg137Ter) single nucleotide variant Pathogenic rs746709222 GRCh38 Chromosome 7, 141614164: 141614164
18 AGK NM_018238.3(AGK): c.424-3C> G single nucleotide variant Pathogenic rs766413410 GRCh37 Chromosome 7, 141315268: 141315268
19 AGK NM_018238.3(AGK): c.424-3C> G single nucleotide variant Pathogenic rs766413410 GRCh38 Chromosome 7, 141615468: 141615468
20 AGK NM_018238.3(AGK): c.3G> C (p.Met1Ile) single nucleotide variant Pathogenic rs863223895 GRCh37 Chromosome 7, 141255269: 141255269
21 AGK NM_018238.3(AGK): c.3G> C (p.Met1Ile) single nucleotide variant Pathogenic rs863223895 GRCh38 Chromosome 7, 141555469: 141555469
22 AGK NM_018238.3(AGK): c.17A> G (p.Lys6Arg) single nucleotide variant Benign/Likely benign rs148294392 GRCh37 Chromosome 7, 141255283: 141255283
23 AGK NM_018238.3(AGK): c.17A> G (p.Lys6Arg) single nucleotide variant Benign/Likely benign rs148294392 GRCh38 Chromosome 7, 141555483: 141555483
24 AGK NM_018238.3(AGK): c.803C> A (p.Thr268Asn) single nucleotide variant Uncertain significance rs142779190 GRCh37 Chromosome 7, 141341124: 141341124
25 AGK NM_018238.3(AGK): c.803C> A (p.Thr268Asn) single nucleotide variant Uncertain significance rs142779190 GRCh38 Chromosome 7, 141641324: 141641324
26 AGK NM_018238.3(AGK): c.863C> T (p.Ala288Val) single nucleotide variant Conflicting interpretations of pathogenicity rs763068104 GRCh37 Chromosome 7, 141341184: 141341184
27 AGK NM_018238.3(AGK): c.863C> T (p.Ala288Val) single nucleotide variant Conflicting interpretations of pathogenicity rs763068104 GRCh38 Chromosome 7, 141641384: 141641384
28 AGK NM_018238.3(AGK): c.1088C> T (p.Thr363Met) single nucleotide variant Uncertain significance rs142069429 GRCh37 Chromosome 7, 141351366: 141351366
29 AGK NM_018238.3(AGK): c.1088C> T (p.Thr363Met) single nucleotide variant Uncertain significance rs142069429 GRCh38 Chromosome 7, 141651566: 141651566
30 AGK NM_018238.3(AGK): c.-139G> A single nucleotide variant Uncertain significance rs886062017 GRCh38 Chromosome 7, 141551310: 141551310
31 AGK NM_018238.3(AGK): c.-139G> A single nucleotide variant Uncertain significance rs886062017 GRCh37 Chromosome 7, 141251110: 141251110
32 AGK NM_018238.3(AGK): c.-75G> C single nucleotide variant Uncertain significance rs560194759 GRCh38 Chromosome 7, 141551374: 141551374
33 AGK NM_018238.3(AGK): c.-75G> C single nucleotide variant Uncertain significance rs560194759 GRCh37 Chromosome 7, 141251174: 141251174
34 AGK NM_018238.3(AGK): c.424-11T> C single nucleotide variant Conflicting interpretations of pathogenicity rs200973491 GRCh37 Chromosome 7, 141315260: 141315260
35 AGK NM_018238.3(AGK): c.424-11T> C single nucleotide variant Conflicting interpretations of pathogenicity rs200973491 GRCh38 Chromosome 7, 141615460: 141615460
36 AGK NM_018238.3(AGK): c.637T> C (p.Ser213Pro) single nucleotide variant Uncertain significance rs886062019 GRCh37 Chromosome 7, 141333749: 141333749
37 AGK NM_018238.3(AGK): c.637T> C (p.Ser213Pro) single nucleotide variant Uncertain significance rs886062019 GRCh38 Chromosome 7, 141633949: 141633949
38 AGK NM_018238.3(AGK): c.*933C> T single nucleotide variant Uncertain significance rs73171606 GRCh37 Chromosome 7, 141353657: 141353657
39 AGK NM_018238.3(AGK): c.*933C> T single nucleotide variant Uncertain significance rs73171606 GRCh38 Chromosome 7, 141653857: 141653857
40 AGK NM_018238.3(AGK): c.*967T> C single nucleotide variant Uncertain significance rs886062026 GRCh37 Chromosome 7, 141353691: 141353691
41 AGK NM_018238.3(AGK): c.*967T> C single nucleotide variant Uncertain significance rs886062026 GRCh38 Chromosome 7, 141653891: 141653891
42 AGK NM_018238.3(AGK): c.*1024C> T single nucleotide variant Uncertain significance rs78124534 GRCh37 Chromosome 7, 141353748: 141353748
43 AGK NM_018238.3(AGK): c.*1024C> T single nucleotide variant Uncertain significance rs78124534 GRCh38 Chromosome 7, 141653948: 141653948
44 AGK NM_018238.3(AGK): c.*1308_*1311delAATT deletion Uncertain significance rs886062029 GRCh37 Chromosome 7, 141354032: 141354035
45 AGK NM_018238.3(AGK): c.*1308_*1311delAATT deletion Uncertain significance rs886062029 GRCh38 Chromosome 7, 141654232: 141654235
46 AGK NM_018238.3(AGK): c.-88G> C single nucleotide variant Uncertain significance rs886062018 GRCh37 Chromosome 7, 141251161: 141251161
47 AGK NM_018238.3(AGK): c.-88G> C single nucleotide variant Uncertain significance rs886062018 GRCh38 Chromosome 7, 141551361: 141551361
48 AGK NM_018238.3(AGK): c.743A> C (p.His248Pro) single nucleotide variant Uncertain significance rs150160397 GRCh38 Chromosome 7, 141641264: 141641264
49 AGK NM_018238.3(AGK): c.743A> C (p.His248Pro) single nucleotide variant Uncertain significance rs150160397 GRCh37 Chromosome 7, 141341064: 141341064
50 AGK NM_018238.3(AGK): c.1052G> A (p.Arg351Gln) single nucleotide variant Uncertain significance rs374861637 GRCh37 Chromosome 7, 141351330: 141351330

Expression for Sengers Syndrome

Search GEO for disease gene expression data for Sengers Syndrome.

Pathways for Sengers Syndrome

GO Terms for Sengers Syndrome

Sources for Sengers Syndrome

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62 PubMed
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69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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