61:
29:
242:
with movement. Excess amounts of T3 circulate in the bloodstream. It is unclear if this is a consequence of compensatory hyperdeiodination or if it results from impaired uptake by certain cell types. Increased T3 levels in the blood may be toxic to some organs and contribute to the signs and symptoms of Allan–Herndon–Dudley syndrome.
780:
Groeneweg, S; Peeters, RP; Moran, C; Stoupa, A; Auriol, F; Tonduti, D; Dica, A; Paone, L; Rozenkova, K; Malikova, J; van der Walt, A; de Coo, IFM; McGowan, A; Lyons, G; Aarsen, FK; Barca, D; van Beynum, IM; van der Knoop, MM; Jansen, J; Manshande, M; Lunsing, RJ; Nowak, S; den Uil, CA; Zillikens, MC;
310:(triiodothyroacetate or tiratricol, a natural non-classical thyroid hormone) to be beneficial. In 2014, a case was demonstrated in which therapy with TRIAC in early childhood led to significant improvement of cognition and mobility. A first clinical trial demonstrated TRIAC to be safe and effective.
241:
Gene mutations alter the structure and function of the SLC16A2 protein. As a result, this protein is unable to transport T3 into nerve cells effectively. A lack of this critical hormone in certain parts of the brain disrupts normal brain development, resulting in intellectual disability and problems
183:
pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two
781:
Visser, FE; Vrijmoeth, P; de Wit, MCY; Wolf, NI; Zandstra, A; Ambegaonkar, G; Singh, Y; de Rijke, YB; Medici, M; Bertini, ES; Depoorter, S; Lebl, J; Cappa, M; De
Meirleir, L; Krude, H; Craiu, D; Zibordi, F; Oliver Petit, I; Polak, M; Chatterjee, K; Visser, TJ; Visser, WE (September 2019).
192:
mutations have normal intelligence and do not experience problems with movement. Some carriers have been diagnosed with thyroid disease, a condition which is relatively common in the general population. It is unclear whether thyroid disease is related to SLC16A2 mutations in these cases.
184:
X chromosomes), a mutation must be present in both copies of the gene to cause the disorder. Males are affected by X-linked recessive disorders much more frequently than females. A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.
245:
The signature of low T4 and high T3 was for a long time assumed to be caused by either compensatory hyperdeiodination or impaired uptake of T3 in target tissues. A third hypotheses suggested it to ensue from impaired outward transport of thyroxine from thyroid cells and subsequently
118:, results from a mutation of the thyroid hormone transporter MCT8 (also referred to as SLC16A2). Consequently, thyroid hormones are unable to enter the nervous system, which depends on thyroid signaling for proper function and development.
509:
Schupper, A; Barash, G; Benyamini, L; Ben-Haim, R; Heyman, E; Lahat, E; Bassan, H (May 2023). "Simple
Evaluation of Thyroid Function Leading to the Diagnosis of Allan-Herndon-Dudley Syndrome, a Rare Neurodevelopmental Disorder".
126:
It is estimated that 80–99% of people with Allan–Herndon–Dudley syndrome will have biparietal narrowing (narrowing of skull), ataxia, abnormalities of the neck, and both absent speech development and aphasia. Weak muscle tone
187:
In X-linked recessive inheritance, a female with one altered copy of the gene in each cell is called a carrier. She can pass on the mutated gene, but usually does not experience signs and symptoms of the disorder. Carriers of
293:
as well are known to play a critical role during early and fetal development, the administration of silymarin during pregnancy is especially thought to be dangerous, potentially leading to the Allan–Herndon–Dudley syndrome.
302:
In May 2013, the US FDA granted Orphan drug status to
Diiodothyropropionic acid (DITPA) in the treatment of MCT8 deficiency. This was following the use of DITPA towards a child in Australia, under compassionate grounds.
686:
Verge, Charles F.; Konrad, Daniel; Cohen, Michal; Di Cosmo, Caterina; Dumitrescu, Alexandra M.; Marcinkowski, Teresa; Hameed, Shihab; Hamilton, Jill; Weiss, Roy E.; Refetoff, Samuel (2012).
238:) where cell-to-cell communication occurs. T3 and other forms of thyroid hormone also help regulate the development of other organs and control the rate of chemical reactions in the body.
912:
783:"Effectiveness and safety of the tri-iodothyronine analogue Triac in children and adults with MCT8 deficiency: an international, single-arm, open-label, phase 2 trial"
368:
Allan, William; Herndon, C. N.; Dudley, Florence C. (1944). "Some examples of the inheritance of mental deficiency: apparently sex-linked idiocy and microcephaly".
637:
Johannes, Jörg; Jayarama-Naidu, Roopa; Meyer, Franziska; Wirth, Eva Katrin; Schweizer, Ulrich; Schomburg, Lutz; Köhrle, Josef; Renko, Kostja (24 February 2016).
1439:
143:), muscle weakness, and involuntary movements of the arms and legs. Many people with Allan–Herndon–Dudley syndrome are unable to walk independently and become
285:
transporter. Due to the essential role played by the thyroid hormone in human metabolism in general it is believed that the intake of silymarin can lead to
1454:
1300:
1063:
905:
1338:
862:
139:, which restrict the movement of certain joints, are common as people age. Mobility is further limited by abnormal muscle stiffness (
898:
737:
TRIAC treatment of an infant with Allan-Herndon-Dudley
Syndrome (AHDS): Effects on iodothyronines in serum and cerebrospinal fluid
1444:
1082:
941:
1419:
639:"Silychristin, a Flavonolignan Derived From the Milk Thistle, Is a Potent Inhibitor of the Thyroid Hormone Transporter MCT8"
1287:
1205:
1138:
290:
282:
274:
262:
1367:
1017:
281:, one of the compounds of the silymarin mixture seems to be perhaps the most powerful and selective inhibitor for the
111:
77:
1305:
1185:
1110:
1049:
588:"Mathematical modeling and simulation of thyroid homeostasis: Implications for the Allan-Herndon-Dudley syndrome"
246:
substrate-mediated overactivity of intrathyroidal deiodinases. This latter hypothesis is supported by results of
387:
327:
1045:
873:
222:. This protein transports a particular hormone into nerve cells in the developing brain. This hormone, called
735:
Iglesias, Ainhoa; Palomares, María; Morte, Beatriz; Obregón, María Jesús; Bernal, Juan (September 10, 2014).
1352:
1295:
1233:
1104:
989:
104:
1003:
833:
740:
1381:
1310:
1262:
925:
388:"Allan-Herndon-Dudley syndrome | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program"
328:"Allan-Herndon-Dudley syndrome | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program"
890:
132:
135:) are common in children with Allan–Herndon–Dudley syndrome. Development of joint deformities called
834:
GeneReviews/NCBI/NIH/UW entry on MCT8 (SLC16A2)-Specific
Thyroid Hormone Cell Transporter Deficiency
60:
1068:
838:
251:
218:, provides instructions for making a protein that plays a critical role in the development of the
1449:
768:
180:
1177:
1191:
812:
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619:
568:
519:
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41:
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609:
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481:
473:
462:"Monocarboxylate transporter 8 deficiency: update on clinical characteristics and treatment"
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28:
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277:
transmembrane transporter. The authors of several studies noted that especially
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623:
572:
523:
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539:"Understanding the hypothalamus-pituitary-thyroid axis in mct8 deficiency"
703:
655:
638:
257:
Several studies have documented the potentially dangerous effects of the
235:
168:
854:
748:
413:"The MCT8 thyroid hormone transporter and Allan-Herndon-Dudley syndrome"
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1346:
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1256:
1242:
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1011:
961:
688:"Diiodothyropropionic Acid (DITPA) in the Treatment of MCT8 Deficiency"
227:
203:
554:
1146:
1132:
1090:
1076:
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1025:
955:
417:
Best
Practice & Research. Clinical Endocrinology & Metabolism
269:
compounds found in the silymarin mixture seem to block the uptake of
69:
230:. T3 appears to be critical for the normal formation and growth of
997:
983:
969:
100:
1405:
1400:
867:
207:
894:
234:, as well as the development of junctions between nerve cells (
110:
Allan–Herndon–Dudley syndrome, which is named eponymously for
155:
The typical hormonal signature of AHDS is marked by low free
739:. 38th Annual Meeting of the European Thyroid Association.
36:
This condition is inherited in an X-linked recessive manner
163:
concentration, which translates to increased calculated
692:
The
Journal of Clinical Endocrinology & Metabolism
460:
van Geest, FS; Groeneweg, S; Visser, WE (March 2021).
586:
Wolff, TM; Veil, C; Dietrich, JW; Müller, MA (2022).
844:
1392:
1273:
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103:development that causes both moderate to severe
906:
8:
273:into the cells by selectively blocking the
913:
899:
891:
845:
59:
27:
18:
1406:Mitochondrial pyruvate carrier deficiency
806:
711:
654:
613:
603:
562:
485:
436:
411:Schwartz, CE; Stevenson, RE (June 2007).
210:cause Allan–Herndon–Dudley syndrome. The
99:is a rare X-linked inherited disorder of
787:The Lancet. Diabetes & Endocrinology
131:) and underdevelopment of many muscles (
1301:Recessive multiple epiphyseal dysplasia
1064:Congenital endothelial dystrophy type 2
649:(4). The Endocrine Society: 1694–1701.
319:
289:. Because the thyroid hormones and the
107:and problems with speech and movement.
767:for "Triac Trial in MCT8 Patients" at
512:The Israel Medical Association Journal
370:American Journal of Mental Deficiency
306:Theoretical considerations suggested
7:
1440:Membrane transport protein disorders
179:This condition is inherited in an
14:
537:Müller, J; Heuer, H (July 2012).
287:disruptions of the thyroid system
1455:Diseases named after discoverers
1111:Thyroid dyshormonogenesis type 1
1288:Multiple epiphyseal dysplasia 4
1083:Glucose-galactose malabsorption
841:at National Library of Medicine
1:
1220:Allan–Herndon–Dudley syndrome
1139:Lysinuric protein intolerance
839:Allan–Herndon–Dudley syndrome
799:10.1016/S2213-8587(19)30155-X
97:Allan–Herndon–Dudley syndrome
22:Allan–Herndon–Dudley syndrome
1368:Acrodermatitis enteropathica
1018:Arterial tortuosity syndrome
159:and normal or elevated free
1050:Hereditary elliptocytosis 4
1471:
1046:Hereditary spherocytosis 4
592:Frontiers in Endocrinology
478:10.1007/s12020-020-02603-y
429:10.1016/j.beem.2007.03.009
226:or T3, is produced by the
114:, Florence C. Dudley, and
1415:
1306:Atelosteogenesis, type II
605:10.3389/fendo.2022.882788
392:rarediseases.info.nih.gov
332:rarediseases.info.nih.gov
35:
26:
879:C537047 C537047, C537047
543:European Thyroid Journal
265:transporter. All of the
990:Fanconi-Bickel syndrome
147:-reliant by adulthood.
105:intellectual disability
1445:Neurogenetic disorders
1004:Fructose malabsorption
761:Clinical trial number
741:Santiago de Compostela
1420:solute carrier family
1382:African iron overload
1311:Diastrophic dysplasia
1353:Von Gierke's disease
1234:Von Gierke's disease
704:10.1210/jc.2012-2556
656:10.1210/en.2015-1933
252:computer simulations
214:gene, also known as
151:Endocrine phenotype
1069:Fuchs' dystrophy 4
769:ClinicalTrials.gov
181:X-linked recessive
122:Signs and symptoms
82:Florence C. Dudley
1427:
1426:
1192:Gitelman syndrome
948:Episodic ataxia 6
888:
887:
555:10.1159/000339474
250:experiments with
201:Mutations in the
133:muscle hypoplasia
94:
93:
16:Medical condition
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1325:Pendred syndrome
1097:Renal glycosuria
922:Genetic disorder
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271:thyroid hormones
224:triiodothyronine
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1293:Achondrogenesis
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1178:Crohn's disease
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1125:Hartnup disease
976:De Vivo disease
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116:C. Nash Herndon
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357:Who Named It?
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395:. Retrieved
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335:. Retrieved
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279:silychristin
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240:
215:
211:
202:
200:
197:Pathogenesis
189:
186:
178:
154:
137:contractures
125:
109:
96:
95:
764:NCT02060474
549:(2): 72–9.
232:nerve cells
70:Named after
1434:Categories
1153:Cystinuria
1032:Cystinuria
598:: 882788.
397:2018-04-17
337:2018-04-17
314:References
167:activity (
165:deiodinase
145:wheelchair
141:spasticity
55:pediatrics
1450:Syndromes
1418:see also
928:disorders
665:0013-7227
466:Endocrine
376:: 325–34.
352:synd/1438
298:Treatment
259:silymarin
248:in silico
129:hypotonia
51:neurology
42:Specialty
1355:, GSD-Ib
1236:, GSD-Ic
817:31377265
722:22993035
673:26910310
624:36568087
573:24783000
524:37245112
496:33650046
447:17574010
236:synapses
175:Genetics
169:SPINA-GD
1401:SLC54A1
1376:SLC40A1
1362:SLC39A4
1347:SLC37A4
1339:CDOG 2C
1333:SLC35C1
1319:SLC26A4
1296:type 1B
1282:SLC26A2
1257:SLC17A8
1243:SLC17A5
1228:SLC17A3
1214:SLC16A2
1200:SLC16A1
1186:SLC12A3
1172:SLC11A1
1119:SLC6A19
1058:SLC4A11
1012:SLC2A10
962:SPATCCM
808:7611958
713:3513545
615:9772020
564:3821472
487:8016746
438:2094733
228:thyroid
212:SLC16A2
204:SLC16A2
190:SLC16A2
1263:DFNA25
1147:SLC7A9
1133:SLC7A7
1105:SLC5A5
1091:SLC5A2
1077:SLC5A1
1040:SLC4A1
1026:SLC3A1
998:SLC2A5
984:SLC2A2
970:SLC2A1
956:SLC1A4
942:SLC1A3
868:300523
815:
805:
720:
710:
671:
663:
622:
612:
571:
561:
522:
494:
484:
445:
435:
57:
1393:51-60
1274:21-40
1164:11-20
308:TRIAC
101:brain
1206:HHF7
934:1-10
874:MeSH
863:OMIM
813:PMID
718:PMID
669:PMID
661:ISSN
620:PMID
569:PMID
520:PMID
492:PMID
443:PMID
291:MCT8
283:MCT8
275:MCT8
263:MCT8
216:MCT8
208:gene
803:PMC
795:doi
745:hdl
708:PMC
700:doi
651:doi
647:157
610:PMC
600:doi
559:PMC
551:doi
482:PMC
474:doi
433:PMC
425:doi
355:at
171:).
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470:71
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431:.
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390:.
374:48
372:.
330:.
254:.
161:T3
157:T4
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855:D
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