MCT8 DEFICIENCY
MCID: ALL001
MIFTS: 46

Allan-Herndon-Dudley Syndrome (MCT8 DEFICIENCY) malady

Categories: Genetic diseases, Rare diseases

Aliases & Classifications for Allan-Herndon-Dudley Syndrome

Aliases & Descriptions for Allan-Herndon-Dudley Syndrome:

Name: Allan-Herndon-Dudley Syndrome 54 12 50 25 66 29 13 14 69
Allan-Herndon Syndrome 12 50 25
Ahds 50 66
Mct8 -Specific Thyroid Hormone Cell Transporter Deficiency 25
X-Linked Intellectual Disability with Hypotonia 50
Intellectual Disability and Muscular Atrophy 50
Mental Retardation, X-Linked, with Hypotonia 25
Monocarboxylate Transporter 8 Deficiency 25
Monocarboxylate Transporter-8 Deficiency 50
Monocarboxylate Transporter 8 Deficiency 66
Triiodothyronine Resistence 50
Mct8 Deficiency 66
T3 Resisitence 50

Characteristics:

HPO:

32
allan-herndon-dudley syndrome:
Onset and clinical course congenital onset
Inheritance x-linked dominant inheritance


Classifications:



External Ids:

OMIM 54 300523
Disease Ontology 12 DOID:0050631
MedGen 40 C0795889

Summaries for Allan-Herndon-Dudley Syndrome

UniProtKB/Swiss-Prot : 66 Monocarboxylate transporter 8 deficiency: Consists of a severe form of X-linked psychomotor retardation combined with abnormal thyroid hormone (TH) levels. Thyroid hormone deficiency can be caused by defects of hormone synthesis and action, but it has also been linked to a defect in cellular hormone transport. Affected patients are males with abnormal relative concentrations of three circulating iodothyronines, as well as severe neurological abnormalities, including global developmental delay, central hypotonia, spastic quadriplegia, dystonic movements, rotary nystagmus, and impaired gaze and hearing. Heterozygous females had a milder thyroid phenotype and no neurological defects.

MalaCards based summary : Allan-Herndon-Dudley Syndrome, also known as allan-herndon syndrome, is related to mct8-specific thyroid hormone cell-membrane transporter deficiency and pelizaeus-merzbacher disease, and has symptoms including ataxia, joint stiffness and athetosis. An important gene associated with Allan-Herndon-Dudley Syndrome is SLC16A2 (Solute Carrier Family 16 Member 2), and among its related pathways/superpathways are Blood-Brain Barrier and Immune Cell Transmigration: Pathways Overview and Thyroid hormone signaling pathway. The drugs Ephedrine and Guaifenesin have been mentioned in the context of this disorder. Affiliated tissues include thyroid, brain and bone.

Disease Ontology : 12 An X-linked disease that has material basis in mutation at is in the gene encoding the monocarboxylate transporter-8 which alters the structure and function of the SLC16A2 protein which is then unable to transport the thyroid triiodothyronine (T3) hormone into nerve cells of the developing brain affecting normal brain development resulting in intellectual disability and problems with movement.

Genetics Home Reference : 25 Allan-Herndon-Dudley syndrome is a rare disorder of brain development that causes moderate to severe intellectual disability and problems with movement. This condition, which occurs exclusively in males, disrupts development from before birth. Although affected males have impaired speech and a limited ability to communicate, they seem to enjoy interaction with other people.

NIH Rare Diseases : 50 allan-herndon-dudley syndrome is a disorder of brain development that causes moderate to severe intellectual disability and problems with movement. this condition, which occurs exclusively in males, disrupts development from before birth. although affected males have speech and a limited ability to communicate, they seem to enjoy interaction with others. allan-herndon-dudley syndrome is caused by mutations in the slc16a2 gene. it is inherited in an x-linked recessive manner.  last updated: 6/12/2014

Description from OMIM: 300523

Related Diseases for Allan-Herndon-Dudley Syndrome

Diseases related to Allan-Herndon-Dudley Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

id Related Disease Score Top Affiliating Genes
1 mct8-specific thyroid hormone cell-membrane transporter deficiency 11.6
2 pelizaeus-merzbacher disease 11.4
3 thyroiditis 10.4
4 spasticity 10.3
5 hereditary spastic paraplegia 10.3
6 sensorineural hearing loss 10.3
7 paraplegia 10.3
8 neuronitis 10.3
9 secondary progressive multiple sclerosis 9.8 ZMYM3 ZNF711
10 choroideremia, deafness, and mental retardation 8.9 DACH2 MPP3 SLC16A2 SLCO1C1 ZMYM3 ZNF711

Graphical network of the top 20 diseases related to Allan-Herndon-Dudley Syndrome:



Diseases related to Allan-Herndon-Dudley Syndrome

Symptoms & Phenotypes for Allan-Herndon-Dudley Syndrome

Symptoms by clinical synopsis from OMIM:

300523

Clinical features from OMIM:

300523

Human phenotypes related to Allan-Herndon-Dudley Syndrome:

32 (show top 50) (show all 54)
id Description HPO Frequency HPO Source Accession
1 ataxia 32 HP:0001251
2 joint stiffness 32 HP:0001387
3 athetosis 32 HP:0002305
4 clonus 32 HP:0002169
5 pectus excavatum 32 HP:0000767
6 ptosis 32 HP:0000508
7 hypothyroidism 32 HP:0000821
8 dysarthria 32 HP:0001260
9 hyperreflexia 32 HP:0001347
10 cerebral calcification 32 HP:0002514
11 bowel incontinence 32 HP:0002607
12 scoliosis 32 HP:0002650
13 macrotia 32 HP:0000400
14 pes planus 32 HP:0001763
15 microcephaly 32 HP:0000252
16 neonatal hypotonia 32 HP:0001319
17 flexion contracture 32 HP:0001371
18 feeding difficulties in infancy 32 HP:0008872
19 type i diabetes mellitus 32 HP:0100651
20 spastic tetraplegia 32 HP:0002510
21 intellectual disability, severe 32 HP:0010864
22 skeletal muscle atrophy 32 HP:0003202
23 irritability 32 HP:0000737
24 severe global developmental delay 32 HP:0011344
25 absent speech 32 HP:0001344
26 biparietal narrowing 32 HP:0004422
27 babinski sign 32 HP:0003487
28 inability to walk 32 HP:0002540
29 protruding ear 32 HP:0000411
30 aphasia 32 HP:0002381
31 intellectual disability, progressive 32 HP:0006887
32 narrow face 32 HP:0000275
33 open mouth 32 HP:0000194
34 upslanted palpebral fissure 32 HP:0000582
35 bilateral single transverse palmar creases 32 HP:0007598
36 abnormality of the neck 32 HP:0000464
37 hallux valgus 32 HP:0001822
38 proptosis 32 HP:0000520
39 spastic paraplegia 32 HP:0001258
40 camptodactyly of finger 32 HP:0100490
41 leukodystrophy 32 HP:0002415
42 drooling 32 HP:0002307
43 generalized amyotrophy 32 HP:0003700
44 hypoplasia of the musculature 32 HP:0009004
45 urinary incontinence 32 HP:0000020
46 narrow forehead 32 HP:0000341
47 delayed cns myelination 32 HP:0002188
48 thyroid-stimulating hormone excess 32 HP:0002925
49 stahl ear 32 HP:0100015
50 abnormal conjugate eye movement 32 HP:0000549

UMLS symptoms related to Allan-Herndon-Dudley Syndrome:


ataxia, clonus

Drugs & Therapeutics for Allan-Herndon-Dudley Syndrome

Drugs for Allan-Herndon-Dudley Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 18)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Ephedrine Approved Phase 2 299-42-3 9294
2
Guaifenesin Approved, Vet_approved Phase 2 93-14-1 3516
3
Pseudoephedrine Approved Phase 2 90-82-4 7028
4 Adrenergic Agents Phase 2
5 Adrenergic Agonists Phase 2
6 Adrenergic alpha-Agonists Phase 2
7 Anti-Obesity Agents Phase 2
8 Appetite Depressants Phase 2
9 Autonomic Agents Phase 2
10
Chlorpheniramine Phase 2 113-92-8, 132-22-9 2725
11 Chlorpheniramine, phenylpropanolamine drug combination Phase 2
12 Expectorants Phase 2
13 Hormones Phase 2
14 Nasal Decongestants Phase 2
15 Neurotransmitter Agents Phase 2
16 Peripheral Nervous System Agents Phase 2
17 Respiratory System Agents Phase 2
18 Vasoconstrictor Agents Phase 2

Interventional clinical trials:


id Name Status NCT ID Phase
1 Triac Trial in MCT8 Patients Active, not recruiting NCT02060474 Phase 2
2 Triac Trial II in MCT8 Patients Not yet recruiting NCT02396459 Phase 2

Search NIH Clinical Center for Allan-Herndon-Dudley Syndrome

Genetic Tests for Allan-Herndon-Dudley Syndrome

Genetic tests related to Allan-Herndon-Dudley Syndrome:

id Genetic test Affiliating Genes
1 Allan-Herndon-Dudley Syndrome 29

Anatomical Context for Allan-Herndon-Dudley Syndrome

MalaCards organs/tissues related to Allan-Herndon-Dudley Syndrome:

39
Thyroid, Brain, Bone, Eye, Skeletal Muscle

Publications for Allan-Herndon-Dudley Syndrome

Articles related to Allan-Herndon-Dudley Syndrome:

(show all 25)
id Title Authors Year
1
The Chemical Chaperone Phenylbutyrate Rescues MCT8 Mutations Associated With Milder Phenotypes in Patients With Allan-Herndon-Dudley Syndrome. ( 27977298 )
2017
2
Novel SLC16A2 mutations in patients with Allan-Herndon-Dudley syndrome. ( 27672545 )
2016
3
Clinical and Molecular Characteristics of SLC16A2 (MCT8) Mutations in Three Families with the Allan-Herndon-Dudley Syndrome. ( 27805744 )
2016
4
Comment on "Delayed myelination is not a constant feature of Allan-Herndon-Dudley syndrome: Report of a new case and review of the literature" by Azzolini S et al. Brain & Development 2014;36:716-720. ( 25863745 )
2015
5
Further Insights into the Allan-Herndon-Dudley Syndrome: Clinical and Functional Characterization of a Novel MCT8 Mutation. ( 26426690 )
2015
6
Allan-Herndon-Dudley syndrome with unusual profound sensorineural hearing loss. ( 25850411 )
2015
7
Deletion of exon 1 of the SLC16A2 gene: a common occurrence in patients with Allan-Herndon-Dudley syndrome. ( 25517855 )
2015
8
Clinical and Endocrine Features of Two Allan-Herndon-Dudley Syndrome Patients with Monocarboxylate Transporter 8 Mutations. ( 25896225 )
2015
9
A 7-month-old male with Allan-Herndon-Dudley syndrome and the power of T3. ( 25755011 )
2015
10
Myelination Delay and Allan-Herndon-Dudley Syndrome Caused by a Novel Mutation in the SLC16A2 Gene. ( 25380603 )
2014
11
SLC16A2 mutations in two Japanese patients with Allan-Herndon-Dudley syndrome. ( 27081503 )
2014
12
Clinical course and images of four familial cases of Allan-Herndon-Dudley syndrome with a novel monocarboxylate transporter 8 gene mutation. ( 25160547 )
2014
13
Delayed myelination is not a constant feature of Allan-Herndon-Dudley syndrome: Report of a new case and review of the literature. ( 24268987 )
2013
14
Mutations in MCT8 in patients with Allan-Herndon-Dudley-syndrome affecting its cellular distribution. ( 23550058 )
2013
15
Allan-Herndon-Dudley syndrome (AHDS) in two consecutive generations caused by a missense MCT8 gene mutation. Phenotypic variability with the presence of normal serum T3 levels. ( 23419639 )
2013
16
A Novel Deletion Mutation of SLC16A2 Encoding Monocarboxylate Transporter (MCT) 8 in a 26-year-old Japanese Patient with Allan-Herndon-Dudley Syndrome. ( 24170966 )
2013
17
Allan-Herndon-Dudley syndrome (AHDS) caused by a novel SLC16A2 gene mutation showing severe neurologic features and unexpectedly low TRH-stimulated serum TSH. ( 20713192 )
2010
18
Neuronal 3',3,5-triiodothyronine (T3) uptake and behavioral phenotype of mice deficient in Mct8, the neuronal T3 transporter mutated in Allan-Herndon-Dudley syndrome. ( 19641107 )
2009
19
Allan-Herndon-Dudley syndrome. ( 18589880 )
2008
20
MCT8 mutation analysis and identification of the first female with Allan-Herndon-Dudley syndrome due to loss of MCT8 expression. ( 18398436 )
2008
21
The MCT8 thyroid hormone transporter and Allan-Herndon-Dudley syndrome. ( 17574010 )
2007
22
Decreased cellular uptake and metabolism in Allan-Herndon-Dudley syndrome (AHDS) due to a novel mutation in the MCT8 thyroid hormone transporter. ( 15980113 )
2006
23
Allan-Herndon-Dudley syndrome and the monocarboxylate transporter 8 (MCT8) gene. ( 15889350 )
2005
24
Allan-Herndon-Dudley syndrome: should the locus for this hereditary spastic paraplegia be designated SPG 22? ( 15364700 )
2004
25
Allan-Herndon-Dudley syndrome: clinical and linkage studies on a second family. ( 1605231 )
1992

Variations for Allan-Herndon-Dudley Syndrome

UniProtKB/Swiss-Prot genetic disease variations for Allan-Herndon-Dudley Syndrome:

66 (show all 20)
id Symbol AA change Variation ID SNP ID
1 SLC16A2 p.Ala150Val VAR_022348 rs104894936
2 SLC16A2 p.Leu397Pro VAR_022349 rs122455132
3 SLC16A2 p.Leu438Pro VAR_022350 rs104894931
4 SLC16A2 p.Ser120Phe VAR_059054 rs113994162
5 SLC16A2 p.Val161Met VAR_059056
6 SLC16A2 p.Leu360Trp VAR_059057 rs104894939
7 SLC16A2 p.Gly490Arg VAR_059059 rs794727799
8 SLC16A2 p.Leu494Pro VAR_059060 rs104894938
9 SLC16A2 p.Gly147Arg VAR_074572
10 SLC16A2 p.Ala150Thr VAR_074573 rs373279555
11 SLC16A2 p.Arg197His VAR_074574 rs727504155
12 SLC16A2 p.Gly208Cys VAR_074575
13 SLC16A2 p.Pro247Leu VAR_074576
14 SLC16A2 p.Arg371Cys VAR_074577 rs587784384
15 SLC16A2 p.Asp379Val VAR_074578
16 SLC16A2 p.Pro463Leu VAR_074579
17 SLC16A2 p.Gly484Asp VAR_074580
18 SLC16A2 p.Ser216Phe VAR_075145 rs398124232
19 SLC16A2 p.Leu217Arg VAR_078497
20 SLC16A2 p.Gly490Glu VAR_078498

ClinVar genetic disease variations for Allan-Herndon-Dudley Syndrome:

6 (show all 27)
id Gene Variation Type Significance SNP ID Assembly Location
1 SLC16A2 NM_006517.4(SLC16A2): c.1313T> C (p.Leu438Pro) single nucleotide variant Pathogenic rs104894931 GRCh37 Chromosome X, 73749190: 73749190
2 SLC16A2 SLC16A2, 1-BP DEL, 1212T deletion Pathogenic
3 SLC16A2 NM_006517.4(SLC16A2): c.449C> T (p.Ala150Val) single nucleotide variant Pathogenic rs104894936 GRCh37 Chromosome X, 73740843: 73740843
4 SLC16A2 SLC16A2, EX1DEL deletion Pathogenic
5 SLC16A2 NM_006517.4(SLC16A2): c.1190T> C (p.Leu397Pro) single nucleotide variant Pathogenic rs122455132 GRCh37 Chromosome X, 73749067: 73749067
6 SLC16A2 nsv513796 deletion Pathogenic
7 SLC16A2 NM_006517.4(SLC16A2): c.1481T> C (p.Leu494Pro) single nucleotide variant Pathogenic rs104894938 GRCh37 Chromosome X, 73751249: 73751249
8 SLC16A2 NM_006517.4(SLC16A2): c.1079T> G (p.Leu360Trp) single nucleotide variant Pathogenic rs104894939 GRCh37 Chromosome X, 73745637: 73745637
9 SLC16A2 NM_006517.4(SLC16A2): c.1121C> A (p.Ser374Ter) single nucleotide variant Pathogenic rs104894940 GRCh37 Chromosome X, 73745679: 73745679
10 SLC16A2 NM_006517.4(SLC16A2): c.461_463delTCT (p.Phe156del) deletion Pathogenic/Likely pathogenic rs387906501 GRCh38 Chromosome X, 74521026: 74521028
11 SLC16A2 NM_006517.4(SLC16A2): c.1612delC (p.Pro538Glnfs) deletion Pathogenic rs113994166 GRCh37 Chromosome X, 73751380: 73751380
12 SLC16A2 NM_006517.4(SLC16A2): c.1278_1280delCTT (p.Phe427del) deletion Pathogenic rs113994164 GRCh37 Chromosome X, 73749155: 73749157
13 SLC16A2 NM_006517.4(SLC16A2): c.359C> T (p.Ser120Phe) single nucleotide variant Pathogenic rs113994162 GRCh37 Chromosome X, 73641831: 73641831
14 SLC16A2 NM_006517.4(SLC16A2): c.1253T> C (p.Leu418Pro) single nucleotide variant Pathogenic rs367543059 GRCh37 Chromosome X, 73749130: 73749130
15 SLC16A2 NM_006517.4(SLC16A2): c.277C> T (p.Gln93Ter) single nucleotide variant Pathogenic rs587784386 GRCh37 Chromosome X, 73641749: 73641749
16 SLC16A2 NM_006517.4(SLC16A2): c.449C> A (p.Ala150Glu) single nucleotide variant Likely pathogenic rs104894936 GRCh37 Chromosome X, 73740843: 73740843
17 SLC16A2 NM_006517.4(SLC16A2): c.916C> T (p.Gln306Ter) single nucleotide variant Pathogenic rs587784382 GRCh37 Chromosome X, 73744534: 73744534
18 SLC16A2 NM_006517.4(SLC16A2): c.979G> A (p.Gly327Arg) single nucleotide variant Likely pathogenic rs587784383 GRCh37 Chromosome X, 73744597: 73744597
19 SLC16A2 NM_006517.4(SLC16A2): c.1111C> T (p.Arg371Cys) single nucleotide variant Pathogenic/Likely pathogenic rs587784384 GRCh37 Chromosome X, 73745669: 73745669
20 SLC16A2 NM_006517.4(SLC16A2): c.326G> A (p.Trp109Ter) single nucleotide variant Pathogenic rs794726932 GRCh37 Chromosome X, 73641798: 73641798
21 SLC16A2 NM_006517.4(SLC16A2): c.353A> C (p.His118Pro) single nucleotide variant Likely pathogenic rs794726933 GRCh37 Chromosome X, 73641825: 73641825
22 SLC16A2 NM_006517.4(SLC16A2): c.256delC (p.Arg86Alafs) deletion Pathogenic rs797045965 GRCh37 Chromosome X, 73641728: 73641728
23 SLC16A2 NM_006517.4(SLC16A2): c.374delA (p.Tyr125Serfs) deletion Pathogenic rs797045966 GRCh37 Chromosome X, 73641846: 73641846
24 SLC16A2 NM_006517.4(SLC16A2): c.940C> T (p.Arg314Ter) single nucleotide variant Pathogenic rs766773277 GRCh38 Chromosome X, 74524723: 74524723
25 SLC16A2 NM_006517.4(SLC16A2): c.1392dupC (p.Ile465Hisfs) duplication Pathogenic rs797045962 GRCh38 Chromosome X, 74529434: 74529434
26 SLC16A2 NM_006517.4(SLC16A2): c.1474_1481delGTAATCCT (p.Val492Leufs) deletion Pathogenic rs797045963 GRCh37 Chromosome X, 73751242: 73751249
27 SLC16A2 NM_006517.4(SLC16A2): c.576-1G> A single nucleotide variant Pathogenic rs886042238 GRCh37 Chromosome X, 73744193: 73744193

Expression for Allan-Herndon-Dudley Syndrome

Search GEO for disease gene expression data for Allan-Herndon-Dudley Syndrome.

Pathways for Allan-Herndon-Dudley Syndrome

GO Terms for Allan-Herndon-Dudley Syndrome

Biological processes related to Allan-Herndon-Dudley Syndrome according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 sodium-independent organic anion transport GO:0043252 8.96 SLC16A2 SLCO1C1
2 thyroid hormone transport GO:0070327 8.62 SLC16A2 SLCO1C1

Molecular functions related to Allan-Herndon-Dudley Syndrome according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 thyroid hormone transmembrane transporter activity GO:0015349 8.62 SLC16A2 SLCO1C1

Sources for Allan-Herndon-Dudley 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 Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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