58:
451:. In these cases, hearing loss normally appears before the onset of diabetes and is marked by a decrease in perception of high tone frequencies. The associated hearing loss with diabetes is typically more common and more quickly declining in men than in women.
442:
at position 3243 present symptoms of diabetes. The average age at which people who have MIDD are typically diagnosed is 37 years old but has been seen to range anywhere between 11 years to 68 years old. Of these people with diabetes carrying the
1463:
50:
Diabetes mellitus and deafness, maternally inherited, (MIDD); Diabetes-deafness syndrome, maternally transmitted; Ballinger-Wallace syndrome; Noninsulin-dependent diabetes mellitus with deafness; Diabetes mellitus, type II, with
1376:
Yamasoba T, Oka Y, Tsukuda K, Nakamura M, Kaga K (January 1996). "Auditory findings in patients with maternally inherited diabetes and deafness harboring a point mutation in the mitochondrial transfer RNA(Leu) (UUR) gene".
877:
Murphy R, Turnbull DM, Walker M, Hattersley AT (April 2008). "Clinical features, diagnosis and management of maternally inherited diabetes and deafness (MIDD) associated with the 3243A>G mitochondrial point mutation".
921:
de
Andrade PB, Rubi B, Frigerio F, van den Ouweland JM, Maassen JA, Maechler P (August 2006). "Diabetes-associated mitochondrial DNA mutation A3243G impairs cellular metabolic pathways necessary for beta cell function".
75:
Noninsulin-dependent diabetes, deafness, may also have systemic symptoms including eye, muscle, brain, kidney, heart, and gastrointestinal abnormalities, rarely endocrine abnormalities and osteoporosis
1685:
974:
Maassen JA, 'T Hart LM, Van Essen E, Heine RJ, Nijpels G, Jahangir
Tafrechi RS, et al. (February 2004). "Mitochondrial diabetes: molecular mechanisms and clinical presentation".
791:
Initially, the person is treated by dietary changes and hypoglycaemic agents. This does not last long before the person has to be started on insulin (within 2 years of diagnosis).
1334:"The diabetes-associated 3243 mutation in the mitochondrial tRNA(Leu(UUR)) gene causes severe mitochondrial dysfunction without a strong decrease in protein synthesis rate"
1164:
Uimonen S, Moilanen JS, Sorri M, Hassinen IE, Majamaa K (April 2001). "Hearing impairment in patients with 3243A-->G mtDNA mutation: phenotype and rate of progression".
1563:
1664:
1622:
328:
171:. Some individuals also experience more systemic symptoms including eye, muscle, brain, kidney, heart, and gastrointestinal abnormalities, similar to other
522:
modification, which is decreased as a result of the improper structure of the tRNALeu(UUR). Incorrect tRNALeu(UUR) structure also results in decreased
1580:
1617:
234:
is spared. Thus, patients often have good visual acuity. However, over time the areas of atrophy expand with eventual loss of central vision.
155:
at position 3243A>G, in gene MT-TL1 encoding tRNA leucine 1, is most common. Because mitochondrial DNA is contributed to the embryo by the
1556:
657:. Since the age of onset is later in a person's life, it has been suggested that age plays a role in contributing, along with the reduced
211:; however, Type 1-like diabetes is the more common form of the two. MIDD has also been associated with a number of other issues including
778:
have been associated with MIDD. The most common mutation is the 3243A>G transition in the mitochondrial tRNA-leucine 1 gene (MT-TL1).
1478:
360:
1593:
1741:
1786:
1756:
1646:
1588:
1549:
1420:
237:
Table 1: Metabolically active organs that can be affected by the mitochondrial point mutation and the associated complication:
1239:"Taurine as a constituent of mitochondrial tRNAs: new insights into the functions of taurine and human mitochondrial diseases"
297:
1119:"Progression of Retinopathy Secondary to Maternally Inherited Diabetes and Deafness - Evaluation of Predicting Parameters"
1707:
1713:
1068:"The Mutations and Clinical Variability in Maternally Inherited Diabetes and Deafness: An Analysis of 161 Patients"
448:
258:
227:
184:
168:
1640:
708:
567:
167:
is inherited from maternal family members only. As indicated by the name, MIDD is characterized by diabetes and
1489:
342:
216:
688:
dysfunction. Although the mechanism by which the mutation in the tRNALeu(UUR) causes this dysfunction of the
346:
1632:
743:
739:
716:
712:
658:
646:
630:
614:
610:
583:
382:
99:
692:
is still under investigation, it has been hypothesized that it involves the ion pumps required for sound
1572:
1529:
662:
650:
634:
386:
301:
172:
104:
704:
320:
693:
499:
305:
1210:
Wittenhagen LM, Kelley SO (August 2002). "Dimerization of a pathogenic human mitochondrial tRNA".
514:
first position of the tRNALeu(UUR) is normally post- transcriptionally modified to ensure correct
1402:
1189:
1146:
903:
559:
70:
28:
653:
ratio, this channel cannot function properly and this can result in a person being deficient in
746:, these concentration gradients are not maintained and this can lead to cell death in both the
1781:
1776:
1500:
1394:
1355:
1309:
1268:
1219:
1181:
1138:
1099:
1043:
991:
939:
895:
697:
681:
606:
602:
579:
571:
563:
543:
531:
503:
491:
479:
444:
439:
406:
136:
17:
1690:
1386:
1345:
1299:
1258:
1250:
1173:
1130:
1089:
1079:
1033:
1025:
983:
931:
887:
747:
727:
723:
547:
582:, due to the presence of the A3243G mutation. However, in other people, the same amount of
57:
763:
551:
463:
332:
231:
208:
204:
715:. Naturally, the most metabolically active organs in a person will be affected by this
1727:
1657:
1652:
1612:
1604:
1094:
1067:
1038:
1013:
586:
are generated, but their stability is compromised due to the improper incorporation of
523:
364:
220:
152:
1263:
1238:
637:
regulate the opening and closing of the KATP channel, which controls the secretion of
1770:
1390:
1150:
1117:
Müller PL, Treis T, Pfau M, Esposti SD, Alsaedi A, Maloca P, et al. (May 2020).
907:
891:
595:
495:
1406:
1193:
677:
642:
617:
could have detrimental effects on other processes in the body. One such process is
459:
416:
396:
266:
1118:
987:
1494:
587:
483:
324:
200:
192:
160:
1505:
1472:
1134:
1084:
935:
751:
731:
696:. As the mutation in the tRNALeu(UUR) leads to unbalanced amounts or unstable
626:
622:
601:. This is a result of the mutated tRNALeu(UUR) with its decreased function in
350:
309:
285:
188:
1350:
1333:
1304:
1287:
735:
511:
494:
at position 3243, which encodes tRNALeu(UUR). This mutation is typically in
199:
which progressively declines, over the years, to severe hearing loss at all
196:
1359:
1272:
1254:
1223:
1185:
1142:
1103:
1047:
995:
943:
899:
1398:
1313:
1177:
526:. The mutation has also been shown to result in decreased function of the
1541:
1524:
1066:
Yang M, Xu L, Xu C, Cui Y, Jiang S, Dong J, et al. (November 2021).
805:
800:
575:
487:
435:
289:
132:
1455:
1029:
738:
to regulate the concentration of ions including K+, Na+, and Ca2+ using
720:
700:
689:
685:
666:
654:
638:
618:
519:
507:
281:
252:
164:
139:, which consists of a circular genome. It is associated with the genes
1014:"The Tip of the Iceberg in Maternally Inherited Diabetes and Deafness"
546:
can be present in any tissue, however, it is more commonly present in
1735:
1467:
771:
591:
555:
293:
212:
156:
140:
84:
834:
27:"MIDD" redirects here. For the liberal arts college in Vermont, see
605:. A decrease in function of the respiratory chain as a result of a
203:. The diabetes that accompanies the hearing loss can be similar to
1721:
775:
767:
598:
515:
475:
471:
467:
148:
144:
92:
88:
65:
This condition is inherited via a mitochondrial inheritance manner
1237:
Suzuki T, Suzuki T, Wada T, Saigo K, Watanabe K (December 2002).
719:
deficiency. Included in these metabolically active organs is the
1483:
527:
226:
In the eye, MIDD is characterized by progressive atrophy of the
1545:
1332:
Janssen GM, Maassen JA, van Den
Ouweland JM (October 1999).
183:
As suggested by the name, patients with MIDD are subject to
1421:"Mitochondrial diabetes - Other types of diabetes mellitus"
1288:"Pathophysiology of the MELAS 3243 transition mutation"
558:. The presence of this mutation can lead to decreased
762:
Physical exams, blood tests, family history, biopsy,
1445:
734:, both essential to sound transduction, make use of
665:
ratio, to the slow deterioration of the function of
570:. In some people, this reduction in function of the
1699:
1673:
1631:
1602:
1579:
1515:
1449:
835:"Diabetes and Deafness, Maternally Inherited; MIDD"
574:is suggested to be caused by unbalanced amounts of
490:. MIDD is caused by an A to G substitution in the
98:
79:
69:
46:
41:
1205:
1203:
498:form. A mutation in this gene (A3243G) causes the
1371:
1369:
1286:Flierl A, Reichmann H, Seibel P (October 1997).
1007:
1005:
438:. Over 85% of people that carry the mutation in
1327:
1325:
1323:
969:
967:
965:
963:
961:
959:
957:
955:
953:
1557:
872:
870:
868:
866:
864:
862:
860:
858:
856:
854:
684:mutation, is seen in the form of progressive
8:
1061:
1059:
1057:
518:recognition. Such modification is known as
1564:
1550:
1542:
1446:
839:Online Mendelian Inheritance in Man (OMIM)
447:mutation at position 3243, 75% experience
239:
121:maternally inherited diabetes and deafness
56:
38:
1425:Diapedia, The Living Textbook of Diabetes
1349:
1303:
1262:
1093:
1083:
1037:
711:are reduced, leading to lower levels of
1012:Finsterer J, Frank M (September 2018).
817:
609:mutation could result in a decrease of
562:as a result of reduced function of the
829:
827:
825:
823:
821:
434:MIDD represents 1% of people who have
187:. This begins with a reduction in the
7:
135:which is caused from a mutation in
1338:The Journal of Biological Chemistry
1292:The Journal of Biological Chemistry
766:. Mutations in mitochondrial genes
455:Effect of mutation on tRNALeu(UUR)
361:Focal segmental glomerulosclerosis
25:
1123:American Journal of Ophthalmology
1391:10.1097/00005537-199601000-00010
892:10.1111/j.1464-5491.2008.02359.x
1647:Mitochondrial encephalomyopathy
742:. Without sufficient levels of
502:to be destabilized, as well as
374:Malabsorption or constipation
298:central nervous system disease
18:Diabetes mellitus and deafness
1:
988:10.2337/diabetes.53.2007.S103
613:production. This decrease in
430:Penetrance and age of onset
319:Macular pattern dystrophy,
302:basal ganglia calcification
42:Diabetes and deafness (DAD)
1803:
1072:Frontiers in Endocrinology
478:play an essential role in
449:sensorineural hearing loss
259:Sensorineural hearing loss
228:retinal pigment epithelium
185:sensorineural hearing loss
169:sensorineural hearing loss
26:
1752:
1212:Nature Structural Biology
1135:10.1016/j.ajo.2020.01.013
1085:10.3389/fendo.2021.728043
936:10.1007/s00125-006-0301-9
709:oxidative phosphorylation
568:oxidative phosphorylation
506:in the tRNALeu(UUR). The
217:gastrointestinal problems
64:
55:
1742:Mohr–Tranebjærg syndrome
1351:10.1074/jbc.274.42.29744
1305:10.1074/jbc.272.43.27189
754:, causing hearing loss.
680:, as caused by the 3243
673:Deafness characteristics
641:. When mutations in the
621:secretion by pancreatic
538:Diabetes characteristics
343:Congestive heart failure
329:external ophthalmoplegia
246:Associated complication
1714:Kjer's optic neuropathy
1581:Carbohydrate metabolism
542:The A3243G mutation in
470:, of which 22 code for
347:ventricular hypertrophy
1787:Mitochondrial diseases
1757:mitochondrial proteins
1573:Mitochondrial diseases
982:(Suppl 1): S103–S109.
584:mitochondrial proteins
383:Mitochondrial myopathy
195:above approximately 5
173:mitochondrial diseases
129:mitochondrial diabetes
100:Differential diagnosis
1178:10.1007/s004390100475
387:peripheral neuropathy
113:Diabetes and deafness
105:Mitochondrial disease
1255:10.1093/emboj/cdf656
1018:Oman Medical Journal
629:, precise levels of
578:that are encoded by
321:macular degeneration
1344:(42): 29744–29748.
1298:(43): 27189–27196.
1030:10.5001/omj.2018.80
500:native conformation
306:cerebral infarction
300:, encephalatrophy,
280:Strokes, seizures,
83:Mutation in either
1516:External resources
566:and a decrease in
560:oxygen consumption
466:which contains 37
179:Signs and symptoms
29:Middlebury College
1764:
1763:
1674:No primary system
1539:
1538:
1385:(1 Pt 1): 49–53.
1249:(23): 6581–6589.
880:Diabetic Medicine
698:respiratory chain
682:mitochondrial DNA
607:mitochondrial DNA
603:protein synthesis
580:mitochondrial DNA
572:respiratory chain
564:respiratory chain
544:mitochondrial DNA
532:protein synthesis
492:mitochondrial DNA
480:protein synthesis
445:mitochondrial DNA
440:mitochondrial DNA
422:
421:
407:Hypoaldosteronism
230:. Initially, the
137:mitochondrial DNA
110:
109:
36:Medical condition
16:(Redirected from
1794:
1691:Pearson syndrome
1566:
1559:
1552:
1543:
1447:
1435:
1434:
1432:
1431:
1417:
1411:
1410:
1379:The Laryngoscope
1373:
1364:
1363:
1353:
1329:
1318:
1317:
1307:
1283:
1277:
1276:
1266:
1243:The EMBO Journal
1234:
1228:
1227:
1207:
1198:
1197:
1161:
1155:
1154:
1114:
1108:
1107:
1097:
1087:
1063:
1052:
1051:
1041:
1009:
1000:
999:
971:
948:
947:
930:(8): 1816–1826.
918:
912:
911:
874:
849:
848:
846:
845:
831:
748:stria vascularis
728:stria vascularis
724:stria vascularis
625:. In pancreatic
482:by transporting
240:
131:is a subtype of
60:
39:
21:
1802:
1801:
1797:
1796:
1795:
1793:
1792:
1791:
1767:
1766:
1765:
1760:
1748:
1695:
1669:
1627:
1598:
1575:
1570:
1540:
1535:
1534:
1511:
1510:
1458:
1444:
1439:
1438:
1429:
1427:
1419:
1418:
1414:
1375:
1374:
1367:
1331:
1330:
1321:
1285:
1284:
1280:
1236:
1235:
1231:
1209:
1208:
1201:
1163:
1162:
1158:
1116:
1115:
1111:
1065:
1064:
1055:
1011:
1010:
1003:
973:
972:
951:
920:
919:
915:
876:
875:
852:
843:
841:
833:
832:
819:
814:
797:
789:
784:
760:
675:
540:
464:circular genome
462:have their own
457:
432:
427:
403:Adrenal glands
323:, proliferated
277:Brain (general)
209:Type 2 diabetes
205:Type 1 diabetes
181:
37:
32:
23:
22:
15:
12:
11:
5:
1800:
1798:
1790:
1789:
1784:
1779:
1769:
1768:
1762:
1761:
1753:
1750:
1749:
1747:
1746:
1745:
1744:
1732:
1731:
1730:
1728:HUPRA syndrome
1718:
1717:
1716:
1703:
1701:
1697:
1696:
1694:
1693:
1688:
1683:
1677:
1675:
1671:
1670:
1668:
1667:
1662:
1661:
1660:
1655:
1643:
1637:
1635:
1629:
1628:
1626:
1625:
1620:
1615:
1609:
1607:
1605:nervous system
1600:
1599:
1597:
1596:
1591:
1585:
1583:
1577:
1576:
1571:
1569:
1568:
1561:
1554:
1546:
1537:
1536:
1533:
1532:
1520:
1519:
1517:
1513:
1512:
1509:
1508:
1497:
1486:
1475:
1459:
1454:
1453:
1451:
1450:Classification
1443:
1442:External links
1440:
1437:
1436:
1412:
1365:
1319:
1278:
1229:
1218:(8): 586–590.
1199:
1172:(4): 284–289.
1166:Human Genetics
1156:
1109:
1053:
1024:(5): 437–440.
1001:
949:
913:
850:
816:
815:
813:
810:
809:
808:
803:
796:
793:
788:
785:
783:
780:
759:
756:
674:
671:
554:rates such as
539:
536:
524:aminoacylation
456:
453:
431:
428:
426:
423:
420:
419:
414:
410:
409:
404:
400:
399:
394:
390:
389:
380:
376:
375:
372:
368:
367:
358:
354:
353:
340:
336:
335:
317:
313:
312:
278:
274:
273:
272:Short stature
270:
262:
261:
256:
248:
247:
244:
243:Organ affected
221:cardiomyopathy
180:
177:
153:point mutation
108:
107:
102:
96:
95:
81:
77:
76:
73:
67:
66:
62:
61:
53:
52:
48:
44:
43:
35:
24:
14:
13:
10:
9:
6:
4:
3:
2:
1799:
1788:
1785:
1783:
1780:
1778:
1775:
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1772:
1759:
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1751:
1743:
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1739:
1738:
1737:
1733:
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1726:
1725:
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1723:
1719:
1715:
1712:
1711:
1710:
1709:
1705:
1704:
1702:
1698:
1692:
1689:
1687:
1684:
1682:
1679:
1678:
1676:
1672:
1666:
1663:
1659:
1656:
1654:
1651:
1650:
1649:
1648:
1644:
1642:
1639:
1638:
1636:
1634:
1630:
1624:
1621:
1619:
1616:
1614:
1613:Leigh disease
1611:
1610:
1608:
1606:
1601:
1595:
1592:
1590:
1587:
1586:
1584:
1582:
1578:
1574:
1567:
1562:
1560:
1555:
1553:
1548:
1547:
1544:
1531:
1527:
1526:
1522:
1521:
1518:
1514:
1507:
1503:
1502:
1498:
1496:
1492:
1491:
1487:
1485:
1481:
1480:
1476:
1474:
1470:
1469:
1465:
1461:
1460:
1457:
1452:
1448:
1441:
1426:
1422:
1416:
1413:
1408:
1404:
1400:
1396:
1392:
1388:
1384:
1380:
1372:
1370:
1366:
1361:
1357:
1352:
1347:
1343:
1339:
1335:
1328:
1326:
1324:
1320:
1315:
1311:
1306:
1301:
1297:
1293:
1289:
1282:
1279:
1274:
1270:
1265:
1260:
1256:
1252:
1248:
1244:
1240:
1233:
1230:
1225:
1221:
1217:
1213:
1206:
1204:
1200:
1195:
1191:
1187:
1183:
1179:
1175:
1171:
1167:
1160:
1157:
1152:
1148:
1144:
1140:
1136:
1132:
1128:
1124:
1120:
1113:
1110:
1105:
1101:
1096:
1091:
1086:
1081:
1077:
1073:
1069:
1062:
1060:
1058:
1054:
1049:
1045:
1040:
1035:
1031:
1027:
1023:
1019:
1015:
1008:
1006:
1002:
997:
993:
989:
985:
981:
977:
970:
968:
966:
964:
962:
960:
958:
956:
954:
950:
945:
941:
937:
933:
929:
925:
917:
914:
909:
905:
901:
897:
893:
889:
886:(4): 383–99.
885:
881:
873:
871:
869:
867:
865:
863:
861:
859:
857:
855:
851:
840:
836:
830:
828:
826:
824:
822:
818:
811:
807:
804:
802:
799:
798:
794:
792:
786:
781:
779:
777:
773:
769:
765:
757:
755:
753:
749:
745:
741:
737:
733:
729:
725:
722:
718:
714:
710:
706:
702:
699:
695:
691:
687:
683:
679:
672:
670:
668:
664:
660:
656:
652:
648:
644:
640:
636:
632:
628:
624:
620:
616:
612:
608:
604:
600:
597:
596:mitochondrial
593:
589:
585:
581:
577:
573:
569:
565:
561:
557:
553:
549:
545:
537:
535:
533:
529:
525:
521:
517:
513:
509:
505:
501:
497:
496:heteroplasmic
493:
489:
485:
481:
477:
473:
469:
465:
461:
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678:Hearing loss
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645:disrupt the
643:mitochondria
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504:dimerization
460:Mitochondria
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417:Osteoporosis
397:Hypogonadism
304:, migraine,
267:Hypothalamus
236:
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764:DNA testing
705:respiration
590:at the UUR
588:amino acids
552:replication
550:with lower
484:amino acids
365:nephropathy
325:retinopathy
201:frequencies
193:frequencies
161:spermatozoa
159:and not by
47:Other names
1771:Categories
1633:Myopathies
1603:Primarily
1501:DiseasesDB
1430:2018-02-06
1078:: 728043.
844:2024-03-02
812:References
752:hair cells
732:hair cells
627:Beta-cells
623:Beta-cells
351:arrhythmia
310:dysarthria
286:cerebellum
189:perception
1755:see also
1151:210935778
908:205548877
782:Treatment
758:Diagnosis
736:ion pumps
530:and thus
512:anticodon
371:Intestine
1782:Deafness
1777:Diabetes
1525:Orphanet
1407:44601058
1360:10514449
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1143:31987901
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795:See also
750:and the
730:and the
721:cochlear
686:cochlear
576:proteins
488:ribosome
474:. These
436:diabetes
425:Genetics
290:cerebrum
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71:Symptoms
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667:B-cells
655:insulin
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548:tissues
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253:cochlea
165:disease
163:, this
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1686:MNGIE
1658:MERRF
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1473:E13.6
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472:tRNAs
468:genes
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647:ATP
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