MIDD
MCID: DBT090
MIFTS: 44

Diabetes and Deafness, Maternally Inherited (MIDD)

Categories: Ear diseases, Endocrine diseases, Eye diseases, Fetal diseases, Metabolic diseases, Rare diseases

Aliases & Classifications for Diabetes and Deafness, Maternally Inherited

MalaCards integrated aliases for Diabetes and Deafness, Maternally Inherited:

Name: Diabetes and Deafness, Maternally Inherited 56 52
Midd 56 52 25 58
Maternally Inherited Diabetes and Deafness 74 52 25
Noninsulin-Dependent Diabetes Mellitus with Deafness 56 25
Diabetes-Deafness Syndrome, Maternally Transmitted 56 52
Diabetes-Deafness Syndrome Maternally Transmitted 29 6
Diabetes Mellitus, Type Ii, with Deafness 56 25
Ballinger-Wallace Syndrome 56 25
Niddm with Deafness 56 25
Maternally Transmitted Diabetes-Deafness Syndrome 25
Maternally-Inherited Diabetes and Hearing Loss 58
Mitochondrial Inherited Diabetes and Deafness 25
Maternally-Inherited Diabetes and Deafness 58
Diabetes Mellitus Type Ii with Deafness 52
Ballinger Wallace Syndrome 52
Mitochondrial Diabetes 58

Characteristics:

Orphanet epidemiological data:

58
maternally-inherited diabetes and deafness
Inheritance: Mitochondrial inheritance; Age of onset: All ages; Age of death: any age;

OMIM:

56
Inheritance:
mitochondrial

Miscellaneous:
variable features
onset of deafness and diabetes in adulthood


HPO:

31
diabetes and deafness, maternally inherited:
Inheritance mitochondrial inheritance


Classifications:

Orphanet: 58  
Rare eye diseases
Rare otorhinolaryngological diseases
Inborn errors of metabolism
Rare endocrine diseases
Developmental anomalies during embryogenesis


Summaries for Diabetes and Deafness, Maternally Inherited

NIH Rare Diseases : 52 Maternally inherited diabetes and deafness (MIDD) is a form of diabetes that is often accompanied by hearing loss , especially of high tones. The diabetes in MIDD is characterized by high blood sugar levels (hyperglycemia) resulting from a shortage of the hormone insulin, which regulates the amount of sugar in the blood. MIDD is caused by mutations in the MT-TL1 , MT-TK , or MT-TE gene . These genes are found in mitochondrial DNA , which is part of cellular structures called mitochondria . Although most DNA is packaged in chromosomes within the cell nucleus , mitochondria also have a small amount of their own DNA (known as mitochondrial DNA or mtDNA). Because the genes involved with MIDD are found in mitochondrial DNA, this condition is inherited in a mitochondrial pattern, which is also known as maternal inheritance. Because egg cells, but not sperm cells, contribute mitochondria to the developing embryo, only females pass mitochondrial conditions to their children. Mitochondrial disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass mitochondrial traits to their children.

MalaCards based summary : Diabetes and Deafness, Maternally Inherited, also known as midd, is related to mitochondrial encephalomyopathy and lactic acidosis. An important gene associated with Diabetes and Deafness, Maternally Inherited is MT-TE (Mitochondrially Encoded TRNA-Glu (GAA/G)), and among its related pathways/superpathways is tRNA Aminoacylation. The drugs Latanoprost and Dexamethasone acetate have been mentioned in the context of this disorder. Affiliated tissues include kidney, heart and eye, and related phenotypes are type ii diabetes mellitus and malabsorption

Genetics Home Reference : 25 Maternally inherited diabetes and deafness (MIDD) is a form of diabetes that is often accompanied by hearing loss, especially of high tones. The diabetes in MIDD is characterized by high blood sugar levels (hyperglycemia) resulting from a shortage of the hormone insulin, which regulates the amount of sugar in the blood. In MIDD, the diabetes and hearing loss usually develop in mid-adulthood, although the age that they occur varies from childhood to late adulthood. Typically, hearing loss occurs before diabetes. Some people with MIDD develop an eye disorder called macular retinal dystrophy, which is characterized by colored patches in the light-sensitive tissue that lines the back of the eye (the retina). This disorder does not usually cause vision problems in people with MIDD. Individuals with MIDD also may experience muscle cramps or weakness, particularly during exercise; heart problems; kidney disease; and constipation. Individuals with MIDD are often shorter than their peers.

OMIM : 56 Maternally inherited diabetes-deafness syndrome (MIDD) is a mitochondrial disorder characterized by onset of sensorineural hearing loss and diabetes in adulthood. Some patients may have additional features observed in mitochondrial disorders, including pigmentary retinopathy, ptosis, cardiomyopathy, myopathy, renal problems, and neuropsychiatric symptoms (Ballinger et al., 1992; Reardon et al., 1992; Guillausseau et al., 2001). The association of diabetes and deafness is observed with Wolfram syndrome (see 222300), Rogers syndrome (249270), and Herrmann syndrome (172500), but all 3 of these disorders have other clinical manifestations. (520000)

Wikipedia : 74 Diabetes and deafness (DAD) or maternally inherited diabetes and deafness (MIDD) or mitochondrial... more...

Related Diseases for Diabetes and Deafness, Maternally Inherited

Diseases related to Diabetes and Deafness, Maternally Inherited via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 96)
# Related Disease Score Top Affiliating Genes
1 mitochondrial encephalomyopathy 29.6 MT-TL1 MT-TK
2 lactic acidosis 29.4 MT-TL1 MT-TK MT-TE
3 chronic progressive external ophthalmoplegia 29.4 MT-TL1 MT-TK
4 mitochondrial disorders 29.2 MT-TL1 MT-TK MT-TE
5 kearns-sayre syndrome 29.2 MT-TL1 MT-TK
6 mitochondrial metabolism disease 29.1 MT-TL1 MT-TK MT-TE
7 mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes 29.1 MT-TL1 MT-TK MT-TE
8 mitochondrial myopathy 29.1 MT-TL1 MT-TK MT-TE
9 myopathy 29.1 MT-TL1 MT-TK MT-TE
10 non-amyloid monoclonal immunoglobulin deposition disease 11.3
11 diabetes mellitus, noninsulin-dependent 10.3
12 hyperglycemia 10.3
13 macular degeneration, age-related, 2 10.2
14 mitochondrial complex iv deficiency 10.2
15 3-methylglutaconic aciduria, type i 10.2
16 cyclic vomiting syndrome 10.2
17 ptosis 10.2
18 microvascular complications of diabetes 5 10.2
19 basal ganglia calcification 10.2
20 intestinal pseudo-obstruction 10.2
21 sensorineural hearing loss 10.2
22 constipation 10.2
23 diabetes mellitus 10.2
24 dowling-degos disease 1 10.1
25 diabetes mellitus, type i 10.1
26 yemenite deaf-blind hypopigmentation syndrome 10.1
27 branchiootic syndrome 1 10.1
28 macular degeneration, age-related, 1 10.1
29 mitochondrial myopathy with diabetes 10.0
30 ataxia and polyneuropathy, adult-onset 10.0
31 maturity-onset diabetes of the young, type 3 10.0
32 gallbladder disease 1 10.0
33 maturity-onset diabetes of the young 10.0
34 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.0
35 chorea, childhood-onset, with psychomotor retardation 10.0
36 common cold 10.0
37 choreatic disease 10.0
38 kidney disease 10.0
39 end stage renal disease 10.0
40 ileus 10.0
41 fundus dystrophy 10.0
42 amyloidosis 10.0
43 hypoaldosteronism 10.0
44 mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes 10.0
45 monogenic diabetes 10.0
46 inherited retinal disorder 10.0
47 premature aging 10.0
48 atrial standstill 1 10.0
49 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant 1 10.0
50 osteogenic sarcoma 10.0

Graphical network of the top 20 diseases related to Diabetes and Deafness, Maternally Inherited:



Diseases related to Diabetes and Deafness, Maternally Inherited

Symptoms & Phenotypes for Diabetes and Deafness, Maternally Inherited

Human phenotypes related to Diabetes and Deafness, Maternally Inherited:

58 31 (show all 35)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 type ii diabetes mellitus 58 31 hallmark (90%) Very frequent (99-80%) HP:0005978
2 malabsorption 58 31 hallmark (90%) Very frequent (99-80%) HP:0002024
3 sensorineural hearing impairment 58 31 hallmark (90%) Very frequent (99-80%) HP:0000407
4 constipation 58 31 hallmark (90%) Very frequent (99-80%) HP:0002019
5 macular dystrophy 58 31 hallmark (90%) Very frequent (99-80%) HP:0007754
6 abnormal chorioretinal morphology 31 hallmark (90%) HP:0000532
7 proteinuria 58 31 frequent (33%) Frequent (79-30%) HP:0000093
8 muscle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0001324
9 hypertrophic cardiomyopathy 58 31 frequent (33%) Frequent (79-30%) HP:0001639
10 arrhythmia 58 31 frequent (33%) Frequent (79-30%) HP:0011675
11 congestive heart failure 58 31 frequent (33%) Frequent (79-30%) HP:0001635
12 myalgia 58 31 frequent (33%) Frequent (79-30%) HP:0003326
13 hypertension 58 31 frequent (33%) Frequent (79-30%) HP:0000822
14 glomerulopathy 58 31 frequent (33%) Frequent (79-30%) HP:0100820
15 aplasia/hypoplasia of the cerebellum 58 31 frequent (33%) Frequent (79-30%) HP:0007360
16 external ophthalmoplegia 58 31 frequent (33%) Frequent (79-30%) HP:0000544
17 abnormal circulating lipid concentration 31 frequent (33%) HP:0003119
18 cataract 58 31 occasional (7.5%) Occasional (29-5%) HP:0000518
19 visual impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0000505
20 renal insufficiency 58 31 occasional (7.5%) Occasional (29-5%) HP:0000083
21 retinopathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0000488
22 ataxia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001251
23 ptosis 31 occasional (7.5%) HP:0000508
24 cardiomyopathy 31 occasional (7.5%) HP:0001638
25 vertigo 31 HP:0002321
26 abnormality of lipid metabolism 58 Frequent (79-30%)
27 dysarthria 31 HP:0001260
28 chorioretinal abnormality 58 Very frequent (99-80%)
29 pigmentary retinopathy 31 HP:0000580
30 retinal degeneration 31 HP:0000546
31 constriction of peripheral visual field 31 HP:0001133
32 unsteady gait 31 HP:0002317
33 vestibular dysfunction 31 HP:0001751
34 hyperglycemia 31 HP:0003074
35 seizure 31 HP:0001250

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
seizures
dysarthria
unsteady gait
dizziness

Laboratory Abnormalities:
hyperglycemia

Cardiovascular Heart:
cardiomyopathy (in some)

Head And Neck Eyes:
external ophthalmoplegia
concentric narrowing of visual fields
pigmentary retinal degeneration
macular pattern dystrophy
normal visual acuity
more
Head And Neck Ears:
deafness, neurosensory
impaired vestibular function

Endocrine Features:
diabetes mellitus (niddm)

Clinical features from OMIM:

520000

Drugs & Therapeutics for Diabetes and Deafness, Maternally Inherited

Drugs for Diabetes and Deafness, Maternally Inherited (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 24)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Latanoprost Approved, Investigational 130209-82-4 5311221 5282380
2
Dexamethasone acetate Approved, Investigational, Vet_approved 1177-87-3
3
Dexamethasone Approved, Investigational, Vet_approved 50-02-2 5743
4
Cyclophosphamide Approved, Investigational 50-18-0, 6055-19-2 2907
5
Melphalan Approved 148-82-3 460612 4053
6
Bortezomib Approved, Investigational 179324-69-7 387447 93860
7 Antihypertensive Agents
8 Pharmaceutical Solutions
9 Ophthalmic Solutions
10 Antibodies
11 Gastrointestinal Agents
12 Hormones
13
protease inhibitors
14 Immunoglobulins, Intravenous
15 Antineoplastic Agents, Hormonal
16 Antiemetics
17 Hormone Antagonists
18 HIV Protease Inhibitors
19 Myeloma Proteins
20 glucocorticoids
21 BB 1101
22 Immunoglobulins
23 Paraproteins
24 Anti-Inflammatory Agents

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 An Exploratory, Double-blind, Randomized, Placebo-controlled, Single-center, Two-way Cross-over Study With KH176 in Patients With the Mitochondrial DNA tRNALeu(UUR) m.3243A>G Mutation and Clinical Signs of Mitochondrial Disease Completed NCT02909400 Phase 2 KH176;placebo
2 A Phase IIb Double-blind, Randomised, Placebo-controlled, Multi-centre, Confirmative Three-way Cross-over Study on Cognitive Function With Two Doses of KH176 in Subjects With a Genetically Confirmed Mitochondrial DNA tRNALeu(UUR) m.3243A>G Mutation. Recruiting NCT04165239 Phase 2 KH176;KH176;Placebo
3 Clinical Characteristics and Prognostic Factors of Mitochondrial nt3243 A>G Mutation in Taiwan Unknown status NCT02114554
4 An Evaluation of the Usability and Patient Tolerability for Microtherapeutic Dosing of Commercially Available Ocular Medication Via the Eyenovia Microdose Delivery System (MiDD) Completed NCT03480906 Latanoprost;Latanoprost
5 Pilot Study of Bortezomib/Dexamethasone (BD), Followed By Autologous Stem Cell Transplantation and Maintenance Bortezomib/Dexamethasone For the Initial Treatment of Monoclonal Immunoglobulin Deposition Disease (MIDD) Associated With Multiple Myeloma and AL Amyloidosis Completed NCT01383759 Bortezomib/Dexamethasone (BD), Followed By Autologous STC & Maintenance Bortezomib/Dexamethasone
6 Can Metagenomic and Metadata be Combined Using Bioinformatics and Computational Biology Methods to Personalise Patient Treatment. Completed NCT03213067

Search NIH Clinical Center for Diabetes and Deafness, Maternally Inherited

Genetic Tests for Diabetes and Deafness, Maternally Inherited

Genetic tests related to Diabetes and Deafness, Maternally Inherited:

# Genetic test Affiliating Genes
1 Diabetes-Deafness Syndrome Maternally Transmitted 29

Anatomical Context for Diabetes and Deafness, Maternally Inherited

MalaCards organs/tissues related to Diabetes and Deafness, Maternally Inherited:

40
Kidney, Heart, Eye, Retina, Cerebellum, Bone, Skeletal Muscle

Publications for Diabetes and Deafness, Maternally Inherited

Articles related to Diabetes and Deafness, Maternally Inherited:

(show top 50) (show all 319)
# Title Authors PMID Year
1
Phenotypic expression of diabetes secondary to a T14709C mutation of mitochondrial DNA. Comparison with MIDD syndrome (A3243G mutation): a case report. 61 6 56
9353617 1997
2
Novel mitochondrial DNA mutation in tRNA(Lys) (8296A-->G) associated with diabetes. 56 6
9571188 1998
3
Clinical phenotypes, insulin secretion, and insulin sensitivity in kindreds with maternally inherited diabetes and deafness due to mitochondrial tRNALeu(UUR) gene mutation. 56 6
8603770 1996
4
Mitochondrial gene mutations and diabetes mellitus. 56 6
8094200 1993
5
Diabetes mellitus associated with a pathogenic point mutation in mitochondrial DNA. 6 56
1360090 1992
6
Mutation in mitochondrial tRNA(Leu)(UUR) gene in a large pedigree with maternally transmitted type II diabetes mellitus and deafness. 56 6
1284550 1992
7
Molecular and functional effects of the T14709C point mutation in the mitochondrial DNA of a patient with maternally inherited diabetes and deafness. 61 6
12393175 2002
8
Maternally inherited diabetes and deafness: a multicenter study. 56 61
11329229 2001
9
Heteroplasmy levels of a mitochondrial gene mutation associated with diabetes mellitus decrease in leucocyte DNA upon aging. 56 61
8829651 1996
10
A Deafness- and Diabetes-associated tRNA Mutation Causes Deficient Pseudouridinylation at Position 55 in tRNAGlu and Mitochondrial Dysfunction. 6
27519417 2016
11
The phenotypic spectrum of fifty Czech m.3243A>G carriers. 6
27296531 2016
12
High risk of severe cardiac adverse events in patients with mitochondrial m.3243A>G mutation. 6
23243073 2013
13
Pearls & oy-sters: maternally inherited diabetes and deafness presenting with ptosis and macular pattern dystrophy. 56
22869689 2012
14
MERRF/MELAS overlap syndrome: a double pathogenic mutation in mitochondrial tRNA genes. 6
20610441 2010
15
Autonomic symptoms in carriers of the m.3243A>G mitochondrial DNA mutation. 6
20697048 2010
16
Helix unwinding and base flipping enable human MTERF1 to terminate mitochondrial transcription. 6
20550934 2010
17
Efficacy of lamotrigine in disabling myoclonus in a patient with an mtDNA A3243G mutation. 6
19349610 2009
18
Protean phenotypic features of the A3243G mitochondrial DNA mutation. 6
19139304 2009
19
The A3243G tRNALeu(UUR) MELAS mutation causes amino acid misincorporation and a combined respiratory chain assembly defect partially suppressed by overexpression of EFTu and EFG2. 6
18753147 2008
20
Pathogenic mitochondrial DNA mutations are common in the general population. 6
18674747 2008
21
Muscle 3243A-->G mutation load and capacity of the mitochondrial energy-generating system. 6
18306232 2008
22
Selection against pathogenic mtDNA mutations in a stem cell population leads to the loss of the 3243A-->G mutation in blood. 6
18252214 2008
23
The A3243G tRNALeu(UUR) mutation induces mitochondrial dysfunction and variable disease expression without dominant negative acting translational defects in complex IV subunits at UUR codons. 6
17656376 2007
24
Prevalence, segregation, and phenotype of the mitochondrial DNA 3243A>G mutation in children. 6
17823937 2007
25
Normal levels of wild-type mitochondrial DNA maintain cytochrome c oxidase activity for two pathogenic mitochondrial DNA mutations but not for m.3243A-->G. 6
17564976 2007
26
Depletion of mitochondrial DNA in leucocytes harbouring the 3243A->G mtDNA mutation. 6
16950816 2007
27
Maternally inherited diabetes and deafness in a North American kindred: tips for making the diagnosis and review of unique management issues. 6
17018649 2006
28
Muscle phenotype and mutation load in 51 persons with the 3243A>G mitochondrial DNA mutation. 6
17172609 2006
29
Retrospective, multicentric study of 180 children with cytochrome C oxidase deficiency. 6
16326995 2006
30
DNA light-strand preferential recognition of human mitochondria transcription termination factor mTERF. 6
16336784 2005
31
MELAS A3243G mitochondrial DNA mutation and age related maculopathy. 6
15629304 2004
32
Familial myopathy: new insights into the T14709C mitochondrial tRNA mutation. 6
15048886 2004
33
Cerebellar ataxia as atypical manifestation of the 3243A>G MELAS mutation. 6
15032978 2004
34
A mitochondrial DNA mutation (A3243G mtDNA) in a family with cyclic vomiting. 6
12905015 2003
35
Mitochondrial DNA haplogroups do not play a role in the variable phenotypic presentation of the A3243G mutation. 6
12612863 2003
36
The level of the mitochondrial mutation A3243G decreases upon ageing in epithelial cells from individuals with diabetes and deafness. 6
11840193 2001
37
Hearing impairment is common in various phenotypes of the mitochondrial DNA A3243G mutation. 6
11708999 2001
38
Mitochondrial DNA mutations and diabetes: another step toward individualized medicine. 56
11329235 2001
39
Association of the T14709C mutation of mitochondrial DNA with maternally inherited diabetes mellitus and/or deafness in an Italian family. 6
11437868 2001
40
Hearing impairment in patients with 3243A-->G mtDNA mutation: phenotype and rate of progression. 6
11379873 2001
41
No correlation between muscle A3243G mutation load and mitochondrial function in vivo. 6
11320187 2001
42
Barth's syndrome-like disorder: a new phenotype with a maternally inherited A3243G substitution of mitochondrial DNA (MELAS mutation). 6
11241464 2001
43
Relative fitness of carriers of the mitochondrial DNA mutation 3243A > G. 6
11175302 2001
44
Identification of mtDNA mutation in a pedigree with gestational diabetes, deafness, Wolff-Parkinson-White syndrome and placenta accreta. 6
11096278 2001
45
Frequency and clinical features of patients with sensorineural hearing loss associated with the A3243G mutation of the mitochondrial DNA in otorhinolaryngic clinics. 6
11587074 2001
46
Decrease of 3243 A-->G mtDNA mutation from blood in MELAS syndrome: a longitudinal study. 6
11085913 2001
47
The mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode syndrome-associated human mitochondrial tRNALeu(UUR) mutation causes aminoacylation deficiency and concomitant reduced association of mRNA with ribosomes. 6
10858457 2000
48
Decreased aminoacylation of mutant tRNAs in MELAS but not in MERRF patients. 6
10699170 2000
49
The diabetes-associated 3243 mutation in the mitochondrial tRNA(Leu(UUR)) gene causes severe mitochondrial dysfunction without a strong decrease in protein synthesis rate. 6
10514449 1999
50
Nonrandom tissue distribution of mutant mtDNA. 56
10405450 1999

Variations for Diabetes and Deafness, Maternally Inherited

ClinVar genetic disease variations for Diabetes and Deafness, Maternally Inherited:

6 ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 MT-TL1 NC_012920.1:m.3243A>GSNV Pathogenic 9589 rs199474657 MT:3243-3243 MT:3243-3243
2 MT-TE NC_012920.1:m.14692A>GSNV Pathogenic 267298 rs879192165 MT:14692-14692 MT:14692-14692
3 MT-TE m.14709T>CSNV Pathogenic/Likely pathogenic 9617 rs121434453 MT:14709-14709 MT:14709-14709
4 MT-TK m.8296A>GSNV Benign 9584 rs118192102 MT:8296-8296 MT:8296-8296

Expression for Diabetes and Deafness, Maternally Inherited

Search GEO for disease gene expression data for Diabetes and Deafness, Maternally Inherited.

Pathways for Diabetes and Deafness, Maternally Inherited

Pathways related to Diabetes and Deafness, Maternally Inherited according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.04 MT-TL1 MT-TK MT-TE

GO Terms for Diabetes and Deafness, Maternally Inherited

Sources for Diabetes and Deafness, Maternally Inherited

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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