337:, seeing a reduction of TK2 activity to less than 32% in people with MDS found with the mutation. Because TK2 plays a key role in the mitochondrial salvage pathways of several deoxyribonucleoside triphosphates (dNTPs), a lowered activity would lead to less cycling of nucleotides. This lack of nucleotide recycling is detrimental since the mitochondria cannot synthesize entirely new deoxynucleotides, and the inner membrane of the mitochondria prevents the negatively charged nucleotides of the cytosol from entering.
107:. These syndromes affect tissue in the muscle, liver, or both the muscle and brain, respectively. The condition is typically fatal in infancy and early childhood, though some have survived to their teenage years with the myopathic variant and some have survived into adulthood with the SUCLA2 encephalomyopathic variant. There is currently no curative treatment for any form of MDDS, though some preliminary treatments have shown a reduction in symptoms.
59:
589:) suggested that the outcome is often poor with early lethality. More recent studies (2015) with 50 people with SUCLA2 mutations, with range of 16 different mutations, show a high variability in outcomes with a number of people surviving into adulthood (median survival was 20 years). There is significant evidence (p = 0.020) that people with
299:
that primarily affects the brain and the gastrointestinal tract, symptoms can emerge any time in the first fifty years of life; most often they emerge before the person turns 20. Weight loss is common as is a lack of the ability of the stomach and intestines to automatically expand and contract and
618:
Liver disease typically progresses to liver failure in affected children with MPV17-related MDS and liver transplantation remains the only treatment option for liver failure. Approximately half of affected children reported did not undergo liver transplantation and died because of progressive liver
287:
that primarily affect the brain and the liver, symptoms emerge shortly after birth or in early infancy, with hypotonia, symptoms of lactic acidosis, enlarged liver, feeding problems, lack of growth, and delay of psychomotor skills. Neurologically, development is slowed or stopped, and epilepsy
304:) – this leads to feeling full after eating only small amounts of food, nausea, acid reflux, All affected individuals develop weight loss and progressive gastrointestinal dysmotility manifesting as early satiety, nausea, diarrhea, vomiting, and stomach pain and swelling. People also develop
615:-related forms result in defects to the liver. Liver dysfunction is progressive in the majority of individuals with both forms of DGUOK-related MDS and is the most common cause of death. For children with the multi-organ form, liver transplantation provides no survival benefit.
565:
related myopathic form results in muscle weakness, rapidly progresses, leading to respiratory failure and death within a few years of onset. The most common cause of death is pulmonary infection. Only a few people have survived to late childhood and adolescence.
346:
gene codes for the beta-subunit of SCS-A. This enzyme catalyzes the synthesis of succinate and coenzyme A into succinyl-CoA, but is also associated with the complex formed by nucleoside diphosphate kinase (NDPK) in the last step of the dNTP salvage pathway.
1599:
1254:
Wang L, Limongelli A, Vila MR, Carrara F, Zeviani M, Eriksson S (January 2005). "Molecular insight into mitochondrial DNA depletion syndrome in two patients with novel mutations in the deoxyguanosine kinase and thymidine kinase 2 genes".
388:
gene encodes for mitochondrial deoxyguanosine kinase (dGK), which catalyzes the phosphorylation of deoxyribonucleosides into nucleotides. POLG encodes for the catalytic subunit pol ÎłA, which is part of mitochondrial DNA polymerase.
1337:
219:
that primarily affect the brain and the liver, the symptoms are similar to those caused by DGUOK and also emerge shortly after birth, generally with fewer and less severe neurological problems. There is a subset of people of
243:
and failure to meet meaningful developmental milestones, usually occur in infancy, after the first year of life, but sometimes as late as the fifth year. Primary symptoms of the disease are developmental delay, progressive
708:
Carrozzo R, Verrigni D, Rasmussen M, de Coo R, Amartino H, Bianchi M, et al. (March 2016). "Succinate-CoA ligase deficiency due to mutations in SUCLA2 and SUCLG1: phenotype and genotype correlations in 71 patients".
968:
This form of MDDS is also called "Alpers' disease", also called "Alpers' syndrome", "Alpers-Huttenlocher syndrome", "progressive sclerosing poliodystrophy", and "progressive infantile poliodystrophy". It is named after
115:
All forms of MDDS are very rare. MDDS causes a wide range of symptoms, which can appear in newborns, infants, children, or adults, depending on the class of MDDS; within each class symptoms are also diverse.
2062:
596:
RRM2B mutations have been reported in 16 infants with severe encephalomyopathic MDS that is associated with early-onset (neonatal or infantile), multi-organ presentation, and mortality during infancy.
320:
that may be inherited from the parents or may form spontaneously during development of the fetus. It is associated with the mutations of mitochondrial genes in the nucleus and several genes including
200:
that primarily affect the brain and the liver, there are two forms. There is an early-onset form in which symptoms arise from problems in many organs in the first week of life, especially symptoms of
1545:
Cámara, Yolanda; González-Vioque, Emiliano; Scarpelli, Mauro; Torres-Torronteras, Javier; MartĂ, Ramon (2013-10-01). "Feeding the deoxyribonucleoside salvage pathway to rescue mitochondrial DNA".
239:
that primarily affect the brain and the liver, the symptoms are very diverse and can emerge anytime from shortly after birth to old age. The first signs of the disease, which include intractable
127:"), tiredness, lack of stamina, and difficulty feeding begin to appear. Some toddlers start to lose control of the muscles in their face, mouth, and throat, and may have difficulty swallowing.
2153:
1719:
1345:
1469:
El-Hattab AW, Li FY, Schmitt E, Zhang S, Craigen WJ, Wong LJ (March 2010). "MPV17-associated hepatocerebral mitochondrial DNA depletion syndrome: new patients and novel mutations".
1863:
288:
emerges, as do sensory problems like loss of eye control and deafness, and neuromuscular problems like a lack of reflexes, muscular atrophy, and twitching, and epilepsy.
2052:
142:
that primarily affect the brain and muscle, hypotonia generally arises in infants before they are 6 months old, their muscles begin wasting away, and there is delay in
2148:
796:
Saito K, Kimura N, Oda N, Shimomura H, Kumada T, Miyajima T, Murayama K, Tanaka M, Fujii T (May 2012). "Pyruvate therapy for mitochondrial DNA depletion syndrome".
1712:
943:
2255:
2100:
2204:
1737:
1422:"Abnormal neurological features predict poor survival and should preclude liver transplantation in patients with deoxyguanosine kinase deficiency"
2240:
2209:
2085:
2032:
1705:
2219:
2024:
2110:
2070:
228:, who in addition to these symptoms also have easily broken bones that do not cause pain, deformed hands or feet, and problems with their
1611:
540:
There are no treatments for MDDS, but some of the symptoms can be managed. For survivors living with MDDS, there are drugs to control
212:. Rarely within this class of already rare diseases, symptoms only relating to liver disease emerge later in infancy or in childhood.
208:
and the associated jaundice and abdominal swelling, and many neurological problems including developmental delays and regression, and
454:
333:
321:
27:
This article is about a group of autosomal recessive disorders. For a similarly abbreviated (MdDS) rare neurological condition, see
2143:
1158:"Deficiency of the ADP-forming succinyl-CoA synthase activity is associated with encephalomyopathy and mitochondrial DNA depletion"
1156:
Elpeleg O, Miller C, Hershkovitz E, Bitner-Glindzicz M, Bondi-Rubinstein G, Rahman S, Pagnamenta A, Eshhar S, Saada A (June 2005).
2214:
2090:
2080:
2037:
1891:
1858:
1838:
990:
619:
failure – the majority during infancy or early childhood. A few children were reported to survive without liver transplantation.
2179:
1370:. In Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, Bird TD, Fong CT, Mefford HC, Smith RJ, Stephens K (eds.).
2245:
1811:
167:
1420:
Dimmock DP, Dunn JK, Feigenbaum A, Rupar A, Horvath R, Freisinger P, Mousson de
Camaret B, Wong LJ, Scaglia F (October 2008).
2095:
2007:
189:
including the head remaining small, delay or regression in moving, and hearing loss. Many body systems are affected. The
2174:
2138:
1833:
257:
146:(learning basic skills like walking, talking, and intentional, coordinated movement). The spine often begins to curve (
301:
868:"Mitochondrial DNA depletion syndromes: review and updates of genetic basis, manifestations, and therapeutic options"
131:
that had been learned may be lost, but generally the functioning of the brain and ability to think are not affected.
1013:
593:
have longer survival rates, which might mean that some of the resulting protein has some residual enzyme activity.
123:, infants generally develop normally, but by around two years of age, symptoms of general muscle weakness (called "
2075:
1960:
1750:
948:
361:
32:
1372:
SUCLA2-Related
Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form, with Mild Methylmalonic Acuduria
170:, hearing loss, stunted growth, and difficulty breathing that can lead to frequent lung infections. Sometime
225:
2250:
1795:
393:
245:
1292:"Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions"
412:
MDDS is diagnosed based on systemic symptoms presenting in infants, followed by a clinical examination and
1729:
1685:
1368:"SUCLA2-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria"
970:
305:
1697:
181:
that primarily affect the brain and muscle, there is again hypotonia in the first months, symptoms of
2118:
2042:
1775:
143:
88:
521:
a form that primarily affects the brain and the gastrointestinal tract associated with mutations in
1946:
1868:
628:
28:
276:
dysfunction may not be present, many people experience liver impairment leading to liver failure.
2047:
1931:
1926:
1921:
1911:
1451:
1394:
1319:
1138:
984:
734:
379:
synthesis in non-proliferating cells. The other form of R2 is expressed only in dividing cells.
420:
levels are common) medical imaging, and usually is finally confirmed and formally identified by
2123:
1906:
1816:
1562:
1527:
1486:
1443:
1375:
1311:
1272:
1236:
1187:
1130:
1113:
Saada A (December 2004). "Deoxyribonucleotides and disorders of mitochondrial DNA integrity".
1095:
1044:
924:
897:
813:
778:
726:
687:
644:
590:
510:
401:
376:
265:
240:
190:
186:
92:
1062:
Wang H, Han Y, Li S, Chen Y, Chen Y, Wang J, Zhang Y, Zhang Y, Wang J, Xia Y, Yuan J (2021).
627:
Nucleoside bypass therapy is an experimental treatment aimed to restore the normal levels of
1848:
1554:
1517:
1478:
1433:
1303:
1264:
1226:
1218:
1177:
1169:
1122:
1085:
1075:
887:
879:
805:
768:
718:
677:
548:
can help with muscle control. Liver transplants may benefit people with liver involvement.
545:
433:
1291:
1035:
Cohen, BH; Chinnery, PF; Copeland, WC (December 18, 2014). Pagon, RA; et al. (eds.). "
2158:
2128:
1406:
581:
related forms result in deformities to the brain. A 2007 study based on 12 cases from the
421:
308:, with weakness and tingling. There are often eye problems, and intellectual disability.
201:
182:
58:
980:
2133:
1823:
1785:
1231:
1206:
1182:
1157:
1090:
1063:
892:
867:
682:
665:
586:
462:
371:
to deoxyribonucleoside diphosphates. The version of R2 encoded by RRM2B is induced by
365:
248:, hypotonia (low muscle tone), spasticity (stiffness of the limbs) possibly leading to
104:
2234:
1981:
632:
582:
487:
441:
368:
205:
100:
1455:
1323:
1142:
1941:
738:
413:
357:
269:
944:"What is Charlie Gard's condition mitochondrial DNA depletion syndrome (or MDDS)?"
66:
Mitochondrial DNA depletion syndrome is inherited in an autosomal recessive manner
1558:
1522:
1505:
1222:
809:
364:, which generates nucleotide precursors required for DNA replication by reducing
1956:
1951:
1896:
1482:
1268:
916:
417:
261:
249:
128:
1290:
Van
Goethem G, Dermaut B, Löfgren A, Martin JJ, Van Broeckhoven C (July 2001).
975:
2000:
1936:
1916:
1901:
1875:
1760:
1367:
883:
773:
756:
722:
17:
1080:
1976:
1971:
1780:
1765:
1126:
291:
In MDDS associated with mutations in the genes associated with mutations in
209:
159:
147:
124:
1566:
1531:
1490:
1447:
1379:
1315:
1276:
1240:
1191:
1134:
1099:
1048:
928:
901:
817:
782:
730:
691:
331:
Myopathic MDS is strongly correlated to a variety of mutations in the gene
1591:
1966:
1755:
1680:
1064:"Mitochondrial DNA Depletion Syndrome and Its Associated Cardiac Disease"
541:
449:
317:
253:
171:
155:
151:
96:
260:, a type of seizure that consists of repeated myoclonic (muscle) jerks.
1770:
1745:
1603:
1438:
1421:
574:
473:
467:
397:
342:
229:
221:
163:
1173:
204:
as well as low blood sugar. Within weeks of birth they can develop
1504:
Viscomi, Carlo; Bottani, Emanuela; Zeviani, Massimo (2015-06-01).
1307:
612:
604:
578:
523:
498:
492:
479:
384:
352:
325:
273:
272:
may also occur. Additionally, although physical signs of chronic
1790:
1661:
1658:
1655:
1652:
1649:
1646:
1643:
1640:
1637:
1634:
1631:
1628:
1625:
1622:
1619:
1616:
608:
504:
372:
1701:
562:
437:
1207:"Defects in mitochondrial DNA replication and human disease"
1506:"Emerging concepts in the therapy of mitochondrial disease"
436:
that share a common pathology — a lack of functioning
2154:
Megalencephalic leukoencephalopathy with subcortical cysts
1389:– via NCBI Bookshelf (National Library of Medicine).
757:"Mitochondrial depletion syndromes in children and adults"
1016:. National Institute of Neurological Disorders and Stroke
915:
Gorman, Gráinne S.; Taylor, Robert W. (April 17, 2014).
95:
in affected tissues. Symptoms can be any combination of
1211:
Critical
Reviews in Biochemistry and Molecular Biology
991:"Peter Huttenlocher, pediatric neurologist, 1931–2013"
798:
Biochimica et
Biophysica Acta (BBA) - General Subjects
1864:
Lesional demyelinations of the central nervous system
585:(where there is a relatively high incidence due to a
360:, codes for one of two versions of the R2 subunit of
1581:
2197:
2167:
2109:
2061:
2023:
2016:
1990:
1884:
1804:
1736:
1671:
1585:
1510:
Biochimica et
Biophysica Acta (BBA) - Bioenergetics
48:
43:
465:and muscle associated with mutations in the genes
193:was associated with this sub form of the disease.
2053:Chronic inflammatory demyelinating polyneuropathy
185:like nausea, vomiting, and rapid deep breathing,
861:
859:
857:
855:
853:
851:
849:
847:
750:
748:
486:a form that primarily affects the brain and the
2149:Leukoencephalopathy with vanishing white matter
845:
843:
841:
839:
837:
835:
833:
831:
829:
827:
703:
701:
154:), and the child often has abnormal movements (
396:(TyMP), succinate-CoA ligase, alpha sub unit (
1713:
761:The Canadian Journal of Neurological Sciences
8:
444:. There are generally four classes of MDDS:
375:, and is required for normal DNA repair and
2020:
1720:
1706:
1698:
1582:
1338:"Depletionssyndrom, mitochondriales (MDS)"
755:Finsterer, J; Ahting, U (September 2013).
57:
40:
2101:Experimental autoimmune encephalomyelitis
1521:
1437:
1230:
1181:
1089:
1079:
891:
772:
681:
264:atrophy may also occur, often leading to
2205:List of multiple sclerosis organizations
31:. For a type of blood cancer (MDS), see
666:"Inherited mitochondrial DNA depletion"
656:
2210:List of people with multiple sclerosis
2086:Neuromyelitis optica spectrum disorder
2033:Neuromyelitis optica spectrum disorder
1402:
1392:
866:El-Hattab AW, Scaglia F (April 2013).
711:Journal of Inherited Metabolic Disease
1374:. University of Washington, Seattle.
923:. University of Washington, Seattle.
917:"RRM2B-Related Mitochondrial Disease"
279:In MDDS associated with mutations in
235:In MDDS associated with mutations in
215:In MDDS associated with mutations in
196:In MDDS associated with mutations in
177:In MDDS associated with mutations in
134:In MDDS associated with mutations in
119:In MDDS associated with mutations in
7:
2185:Mitochondrial DNA depletion syndrome
2071:Acute disseminated encephalomyelitis
73:Mitochondrial DNA depletion syndrome
44:Mitochondrial DNA depletion syndrome
1162:American Journal of Human Genetics
1014:"Alpers' Disease Information Page"
683:10.1203/01.PDR.0000072796.25097.A5
461:a form that primarily affects the
404:(also known as PEO1 and C10orf2).
328:, are known to be related to MDS.
25:
1471:Molecular Genetics and Metabolism
1257:Molecular Genetics and Metabolism
452:associated with mutations in the
91:that cause a significant drop in
2256:Diseases named after discoverers
2215:Multiple sclerosis drug pipeline
2091:Diffuse myelinoclastic sclerosis
2081:Marburg acute multiple sclerosis
2038:Diffuse myelinoclastic sclerosis
1892:Management of multiple sclerosis
1859:Radiologically isolated syndrome
1839:Expanded Disability Status Scale
356:gene, which is expressed in the
1812:Diagnosis of multiple sclerosis
989:Easton, John (19 August 2013).
2096:Tumefactive multiple sclerosis
2008:Research in multiple sclerosis
1728:Demyelinating diseases of the
942:Wheaton, Oliver (2017-07-25).
448:a form that primarily affects
392:Other causes are mutations of
1:
2241:Autosomal recessive disorders
490:associated with mutations in
300:thus move through it (called
89:autosomal recessive disorders
2175:Central pontine myelinolysis
2144:Pelizaeus–Merzbacher disease
2139:Metachromatic leukodystrophy
1834:Clinically isolated syndrome
1805:Investigations and diagnosis
1559:10.1016/j.drudis.2013.06.009
1523:10.1016/j.bbabio.2015.03.001
1366:Ostergaard E (18 May 2017).
1223:10.3109/10409238.2011.632763
810:10.1016/j.bbagen.2011.08.006
258:epilepsia partialis continua
2180:Marchiafava–Bignami disease
1483:10.1016/j.ymgme.2009.10.003
1344:(in German). Archived from
1269:10.1016/j.ymgme.2004.09.005
993:. The University of Chicago
2272:
26:
2076:Balo concentric sclerosis
884:10.1007/s13311-013-0177-6
774:10.1017/S0317167100014852
723:10.1007/s10545-015-9894-9
302:gastrointestinal motility
210:uncontrolled eye movement
65:
56:
1081:10.3389/fcvm.2021.808115
362:ribonucleotide reductase
52:mtDNA depletion syndrome
33:Myelodysplastic syndrome
1127:10.1089/dna.2004.23.797
570:Encephalomyopathic form
394:thymidine phosphorylase
256:. Seizures may include
246:intellectual disability
226:Navajo neurohepatopathy
166:), difficulty feeding,
87:, is any of a group of
2246:Mitochondrial diseases
2017:Demyelinating diseases
1730:central nervous system
1426:Liver Transplantation
1205:Copeland, WC (2012).
1039:-Related Disorders".
2119:Adrenoleukodystrophy
2043:MOG antibody disease
1845:Serological and CSF
1796:Uhthoff's phenomenon
1547:Drug Discovery Today
1115:DNA and Cell Biology
1068:Front Cardiovasc Med
971:Bernard Jacob Alpers
629:deoxyribonucleotides
432:MDDS are a group of
224:descent who develop
144:psychomotor learning
1947:Monomethyl fumarate
1342:Labor Lademannbogen
416:(for example, high
29:Mal de debarquement
2048:Multiple sclerosis
1932:Interferon beta-1b
1927:Interferon beta-1a
1922:Glatiramer acetate
1912:Diroximel fumarate
1885:Approved treatment
1738:Signs and symptoms
1672:External resources
985:Peter Huttenlocher
664:Elpeleg O (2003).
591:missense mutations
316:MDDS is caused by
252:, and progressive
111:Signs and symptoms
105:encephalomyopathic
2228:
2227:
2193:
2192:
2124:Alexander disease
1907:Dimethyl fumarate
1849:Oligoclonal bands
1817:McDonald criteria
1695:
1694:
872:Neurotherapeutics
645:Charlie Gard case
600:Hepatopathic form
434:genetic disorders
191:Charlie Gard case
187:failure to thrive
93:mitochondrial DNA
70:
69:
38:Medical condition
16:(Redirected from
2263:
2021:
1991:Other treatments
1869:Dawson's fingers
1722:
1715:
1708:
1699:
1583:
1571:
1570:
1542:
1536:
1535:
1525:
1501:
1495:
1494:
1466:
1460:
1459:
1441:
1439:10.1002/lt.21556
1417:
1411:
1410:
1404:
1400:
1398:
1390:
1388:
1386:
1363:
1357:
1356:
1354:
1353:
1334:
1328:
1327:
1287:
1281:
1280:
1251:
1245:
1244:
1234:
1202:
1196:
1195:
1185:
1153:
1147:
1146:
1110:
1104:
1103:
1093:
1083:
1059:
1053:
1052:
1032:
1026:
1025:
1023:
1021:
1010:
1004:
1002:
1000:
998:
966:
960:
959:
957:
956:
939:
933:
932:
912:
906:
905:
895:
863:
822:
821:
793:
787:
786:
776:
752:
743:
742:
705:
696:
695:
685:
661:
546:physical therapy
414:laboratory tests
61:
41:
21:
2271:
2270:
2266:
2265:
2264:
2262:
2261:
2260:
2231:
2230:
2229:
2224:
2220:Pathophysiology
2189:
2163:
2159:CAMFAK syndrome
2129:Canavan disease
2105:
2057:
2012:
1986:
1880:
1800:
1732:
1726:
1696:
1691:
1690:
1667:
1666:
1594:
1580:
1575:
1574:
1553:(19): 950–957.
1544:
1543:
1539:
1503:
1502:
1498:
1468:
1467:
1463:
1419:
1418:
1414:
1401:
1391:
1384:
1382:
1365:
1364:
1360:
1351:
1349:
1336:
1335:
1331:
1296:Nature Genetics
1289:
1288:
1284:
1253:
1252:
1248:
1204:
1203:
1199:
1155:
1154:
1150:
1121:(12): 797–806.
1112:
1111:
1107:
1061:
1060:
1056:
1034:
1033:
1029:
1019:
1017:
1012:
1011:
1007:
996:
994:
988:
976:Alpers' disease
967:
963:
954:
952:
941:
940:
936:
914:
913:
909:
865:
864:
825:
795:
794:
790:
754:
753:
746:
707:
706:
699:
663:
662:
658:
653:
641:
625:
602:
572:
559:
554:
538:
430:
422:genetic testing
410:
314:
202:lactic acidosis
183:lactic acidosis
113:
85:Alper's disease
39:
36:
23:
22:
15:
12:
11:
5:
2269:
2267:
2259:
2258:
2253:
2251:Rare syndromes
2248:
2243:
2233:
2232:
2226:
2225:
2223:
2222:
2217:
2212:
2207:
2201:
2199:
2195:
2194:
2191:
2190:
2188:
2187:
2182:
2177:
2171:
2169:
2165:
2164:
2162:
2161:
2156:
2151:
2146:
2141:
2136:
2134:Krabbe disease
2131:
2126:
2121:
2115:
2113:
2107:
2106:
2104:
2103:
2098:
2093:
2088:
2083:
2078:
2073:
2067:
2065:
2059:
2058:
2056:
2055:
2050:
2045:
2040:
2035:
2029:
2027:
2018:
2014:
2013:
2011:
2010:
2005:
2004:
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1994:
1992:
1988:
1987:
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1964:
1961:+hyaluronidase
1954:
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1824:Poser criteria
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1786:Optic neuritis
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1586:Classification
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1578:External links
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1982:Teriflunomide
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981:Who Named It?
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2063:Inflammatory
1942:Mitoxantrone
1776:Incontinence
1679:
1610:
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1546:
1540:
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1499:
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1371:
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633:mitochondria
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369:diphosphates
358:cell nucleus
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270:Hearing loss
250:quadriplegia
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139:
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133:
129:Motor skills
120:
118:
114:
101:hepatopathic
84:
80:
76:
72:
71:
1957:Ocrelizumab
1952:Natalizumab
1897:Alemtuzumab
1041:GeneReviews
921:GeneReviews
670:Pediatr Res
631:(dNTPs) in
168:acid reflux
49:Other names
2235:Categories
2111:Hereditary
2025:Autoimmune
2001:Daclizumab
1937:Laquinimod
1917:Fingolimod
1902:Cladribine
1876:Frexalimab
1761:Dysarthria
1751:Depression
1352:2017-04-14
1074:: 808115.
997:1 November
955:2021-09-24
651:References
306:neuropathy
174:develops.
1977:Siponimod
1972:Ponesimod
1830:Clinical
1781:Nystagmus
1766:Dysphagia
1405:ignored (
1395:cite book
552:Prognosis
536:Treatment
408:Diagnosis
318:mutations
266:blindness
160:athetosis
148:scoliosis
125:hypotonia
97:myopathic
1967:Ozanimod
1756:Diplopia
1681:Orphanet
1567:23817075
1532:25766847
1491:20074988
1456:28819842
1448:18825706
1380:20301762
1324:35417835
1316:11431686
1277:15639197
1241:22176657
1192:15877282
1143:20619194
1135:15684706
1100:35237671
1049:20301791
929:24741716
902:23385875
818:21855607
783:23968935
731:26475597
692:12736387
639:See also
623:Research
542:epilepsy
254:dementia
241:seizures
172:epilepsy
156:dystonia
152:kyphosis
1997:Former
1771:Fatigue
1607:: G71.3
1232:3244805
1183:1196446
1091:8882844
1020:24 July
893:3625391
739:7881205
611:-, and
418:lactate
285:C10orf2
230:corneas
1746:Ataxia
1662:617156
1659:616896
1656:615471
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1650:617184
1647:615084
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474:SUCLG1
468:SUCLA2
450:muscle
400:) and
398:SUCLG1
343:SUCLA2
312:Causes
222:Navajo
164:chorea
140:SUCLG1
136:SUCLA2
83:), or
2198:Other
2168:Other
1686:35698
1452:S2CID
1320:S2CID
1139:S2CID
987:(see
949:Metro
735:S2CID
613:MPV17
605:DGUOK
579:RRM2B
524:ECGF1
508:, or
499:MPV17
493:DGUOK
488:liver
480:RRM2B
477:, or
463:brain
458:gene;
385:DGUOK
377:mtDNA
353:RRM2B
326:FBXL4
293:ECGF1
274:liver
262:Optic
217:MPV17
198:DGUOK
179:RRM2B
103:, or
1791:Pain
1612:OMIM
1563:PMID
1528:PMID
1514:1847
1487:PMID
1444:PMID
1407:help
1387:2020
1376:PMID
1312:PMID
1273:PMID
1237:PMID
1188:PMID
1131:PMID
1096:PMID
1045:PMID
1037:POLG
1022:2017
999:2013
925:PMID
898:PMID
814:PMID
802:1820
779:PMID
727:PMID
688:PMID
609:POLG
577:and
561:The
529:TYMP
516:PEO1
511:TWNK
505:POLG
402:TWNK
382:The
373:TP53
350:The
340:The
297:TYMP
281:PEO1
237:POLG
81:MDDS
1600:ICD
1555:doi
1518:doi
1479:doi
1434:doi
1304:doi
1265:doi
1227:PMC
1219:doi
1178:PMC
1170:doi
1123:doi
1086:PMC
1076:doi
979:at
888:PMC
880:doi
806:doi
769:doi
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678:doi
607:-,
563:TK2
455:TK2
440:in
438:DNA
334:TK2
322:TK2
162:or
150:or
138:or
121:TK2
79:or
77:MDS
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