326:, 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.
96:. 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.
48:
578:) 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
288:
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
607:
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
276:
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
293:) – 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
604:-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.
554:
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.
335:
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.
1588:
1243:
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".
377:
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.
1326:
208:
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
232:
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
697:
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".
957:
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
104:
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.
2051:
585:
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.
309:
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
189:
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
1534:
Cámara, Yolanda; González-Vioque, Emiliano; Scarpelli, Mauro; Torres-Torronteras, Javier; MartĂ, Ramon (2013-10-01). "Feeding the deoxyribonucleoside salvage pathway to rescue mitochondrial DNA".
228:
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
116:"), 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.
2142:
1708:
1334:
1458:
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".
1852:
277:
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.
2041:
131:
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
2137:
785:
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".
1701:
932:
2244:
2089:
2193:
1726:
1411:"Abnormal neurological features predict poor survival and should preclude liver transplantation in patients with deoxyguanosine kinase deficiency"
2229:
2198:
2074:
2021:
1694:
2208:
2013:
2099:
2059:
217:, who in addition to these symptoms also have easily broken bones that do not cause pain, deformed hands or feet, and problems with their
1600:
529:
There are no treatments for MDDS, but some of the symptoms can be managed. For survivors living with MDDS, there are drugs to control
201:. Rarely within this class of already rare diseases, symptoms only relating to liver disease emerge later in infancy or in childhood.
197:
and the associated jaundice and abdominal swelling, and many neurological problems including developmental delays and regression, and
443:
322:
310:
16:
This article is about a group of autosomal recessive disorders. For a similarly abbreviated (MdDS) rare neurological condition, see
2132:
1147:"Deficiency of the ADP-forming succinyl-CoA synthase activity is associated with encephalomyopathy and mitochondrial DNA depletion"
1145:
Elpeleg O, Miller C, Hershkovitz E, Bitner-Glindzicz M, Bondi-Rubinstein G, Rahman S, Pagnamenta A, Eshhar S, Saada A (June 2005).
2203:
2079:
2069:
2026:
1880:
1847:
1827:
979:
608:
failure – the majority during infancy or early childhood. A few children were reported to survive without liver transplantation.
2168:
1359:. In Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, Bird TD, Fong CT, Mefford HC, Smith RJ, Stephens K (eds.).
2234:
1800:
156:
1409:
Dimmock DP, Dunn JK, Feigenbaum A, Rupar A, Horvath R, Freisinger P, Mousson de
Camaret B, Wong LJ, Scaglia F (October 2008).
2084:
1996:
178:
including the head remaining small, delay or regression in moving, and hearing loss. Many body systems are affected. The
2163:
2127:
1822:
246:
135:(learning basic skills like walking, talking, and intentional, coordinated movement). The spine often begins to curve (
290:
857:"Mitochondrial DNA depletion syndromes: review and updates of genetic basis, manifestations, and therapeutic options"
120:
that had been learned may be lost, but generally the functioning of the brain and ability to think are not affected.
1002:
582:
have longer survival rates, which might mean that some of the resulting protein has some residual enzyme activity.
112:, infants generally develop normally, but by around two years of age, symptoms of general muscle weakness (called "
2064:
1949:
1739:
937:
350:
21:
1361:
SUCLA2-Related
Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form, with Mild Methylmalonic Acuduria
159:, hearing loss, stunted growth, and difficulty breathing that can lead to frequent lung infections. Sometime
214:
2239:
1784:
382:
234:
1281:"Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions"
401:
MDDS is diagnosed based on systemic symptoms presenting in infants, followed by a clinical examination and
1718:
1674:
1357:"SUCLA2-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria"
959:
294:
1686:
170:
that primarily affect the brain and muscle, there is again hypotonia in the first months, symptoms of
2107:
2031:
1764:
132:
77:
510:
a form that primarily affects the brain and the gastrointestinal tract associated with mutations in
1935:
1857:
617:
17:
265:
dysfunction may not be present, many people experience liver impairment leading to liver failure.
2036:
1920:
1915:
1910:
1900:
1440:
1383:
1308:
1127:
973:
723:
368:
synthesis in non-proliferating cells. The other form of R2 is expressed only in dividing cells.
409:
levels are common) medical imaging, and usually is finally confirmed and formally identified by
2112:
1895:
1805:
1551:
1516:
1475:
1432:
1364:
1300:
1261:
1225:
1176:
1119:
1102:
Saada A (December 2004). "Deoxyribonucleotides and disorders of mitochondrial DNA integrity".
1084:
1033:
913:
886:
802:
767:
715:
676:
633:
579:
499:
390:
365:
254:
229:
179:
175:
81:
1051:
Wang H, Han Y, Li S, Chen Y, Chen Y, Wang J, Zhang Y, Zhang Y, Wang J, Xia Y, Yuan J (2021).
616:
Nucleoside bypass therapy is an experimental treatment aimed to restore the normal levels of
1837:
1543:
1506:
1467:
1422:
1292:
1253:
1215:
1207:
1166:
1158:
1111:
1074:
1064:
876:
868:
794:
757:
707:
666:
537:
can help with muscle control. Liver transplants may benefit people with liver involvement.
534:
422:
1280:
1024:
Cohen, BH; Chinnery, PF; Copeland, WC (December 18, 2014). Pagon, RA; et al. (eds.). "
2147:
2117:
1395:
570:
related forms result in deformities to the brain. A 2007 study based on 12 cases from the
410:
297:, with weakness and tingling. There are often eye problems, and intellectual disability.
190:
171:
47:
969:
2122:
1812:
1774:
1220:
1195:
1171:
1146:
1079:
1052:
881:
856:
671:
654:
575:
451:
360:
to deoxyribonucleoside diphosphates. The version of R2 encoded by RRM2B is induced by
354:
237:, hypotonia (low muscle tone), spasticity (stiffness of the limbs) possibly leading to
93:
2223:
1970:
621:
571:
476:
430:
357:
194:
89:
1444:
1312:
1131:
1930:
727:
402:
346:
258:
933:"What is Charlie Gard's condition mitochondrial DNA depletion syndrome (or MDDS)?"
55:
Mitochondrial DNA depletion syndrome is inherited in an autosomal recessive manner
1547:
1511:
1494:
1211:
798:
353:, which generates nucleotide precursors required for DNA replication by reducing
1945:
1940:
1885:
1471:
1257:
905:
406:
250:
238:
117:
1279:
Van
Goethem G, Dermaut B, Löfgren A, Martin JJ, Van Broeckhoven C (July 2001).
964:
1989:
1925:
1905:
1890:
1864:
1749:
1356:
872:
762:
745:
711:
1069:
1965:
1960:
1769:
1754:
1115:
280:
In MDDS associated with mutations in the genes associated with mutations in
198:
148:
136:
113:
1555:
1520:
1479:
1436:
1368:
1304:
1265:
1229:
1180:
1123:
1088:
1037:
917:
890:
806:
771:
719:
680:
320:
Myopathic MDS is strongly correlated to a variety of mutations in the gene
1580:
1955:
1744:
1669:
1053:"Mitochondrial DNA Depletion Syndrome and Its Associated Cardiac Disease"
530:
438:
306:
242:
160:
144:
140:
85:
249:, a type of seizure that consists of repeated myoclonic (muscle) jerks.
1759:
1734:
1592:
1427:
1410:
563:
462:
456:
386:
331:
218:
210:
152:
1162:
193:
as well as low blood sugar. Within weeks of birth they can develop
1493:
Viscomi, Carlo; Bottani, Emanuela; Zeviani, Massimo (2015-06-01).
1296:
601:
593:
567:
512:
487:
481:
468:
373:
341:
314:
262:
261:
may also occur. Additionally, although physical signs of chronic
1779:
1650:
1647:
1644:
1641:
1638:
1635:
1632:
1629:
1626:
1623:
1620:
1617:
1614:
1611:
1608:
1605:
597:
493:
361:
1690:
551:
426:
1196:"Defects in mitochondrial DNA replication and human disease"
1495:"Emerging concepts in the therapy of mitochondrial disease"
425:
that share a common pathology — a lack of functioning
2143:
Megalencephalic leukoencephalopathy with subcortical cysts
1378:– via NCBI Bookshelf (National Library of Medicine).
746:"Mitochondrial depletion syndromes in children and adults"
1005:. National Institute of Neurological Disorders and Stroke
904:
Gorman, Gráinne S.; Taylor, Robert W. (April 17, 2014).
84:
in affected tissues. Symptoms can be any combination of
1200:
Critical
Reviews in Biochemistry and Molecular Biology
980:"Peter Huttenlocher, pediatric neurologist, 1931–2013"
787:
Biochimica et
Biophysica Acta (BBA) - General Subjects
1853:
Lesional demyelinations of the central nervous system
574:(where there is a relatively high incidence due to a
349:, codes for one of two versions of the R2 subunit of
1570:
2186:
2156:
2098:
2050:
2012:
2005:
1979:
1873:
1793:
1725:
1660:
1574:
1499:
Biochimica et
Biophysica Acta (BBA) - Bioenergetics
37:
32:
454:and muscle associated with mutations in the genes
182:was associated with this sub form of the disease.
2042:Chronic inflammatory demyelinating polyneuropathy
174:like nausea, vomiting, and rapid deep breathing,
850:
848:
846:
844:
842:
840:
838:
836:
739:
737:
475:a form that primarily affects the brain and the
2138:Leukoencephalopathy with vanishing white matter
834:
832:
830:
828:
826:
824:
822:
820:
818:
816:
692:
690:
143:), and the child often has abnormal movements (
385:(TyMP), succinate-CoA ligase, alpha sub unit (
1702:
750:The Canadian Journal of Neurological Sciences
8:
433:. There are generally four classes of MDDS:
364:, and is required for normal DNA repair and
2009:
1709:
1695:
1687:
1571:
1327:"Depletionssyndrom, mitochondriales (MDS)"
744:Finsterer, J; Ahting, U (September 2013).
46:
29:
2090:Experimental autoimmune encephalomyelitis
1510:
1426:
1219:
1170:
1078:
1068:
880:
761:
670:
253:atrophy may also occur, often leading to
2194:List of multiple sclerosis organizations
20:. For a type of blood cancer (MDS), see
655:"Inherited mitochondrial DNA depletion"
645:
2199:List of people with multiple sclerosis
2075:Neuromyelitis optica spectrum disorder
2022:Neuromyelitis optica spectrum disorder
1391:
1381:
855:El-Hattab AW, Scaglia F (April 2013).
700:Journal of Inherited Metabolic Disease
1363:. University of Washington, Seattle.
912:. University of Washington, Seattle.
906:"RRM2B-Related Mitochondrial Disease"
268:In MDDS associated with mutations in
224:In MDDS associated with mutations in
204:In MDDS associated with mutations in
185:In MDDS associated with mutations in
166:In MDDS associated with mutations in
123:In MDDS associated with mutations in
108:In MDDS associated with mutations in
7:
2174:Mitochondrial DNA depletion syndrome
2060:Acute disseminated encephalomyelitis
62:Mitochondrial DNA depletion syndrome
33:Mitochondrial DNA depletion syndrome
1151:American Journal of Human Genetics
1003:"Alpers' Disease Information Page"
672:10.1203/01.PDR.0000072796.25097.A5
450:a form that primarily affects the
393:(also known as PEO1 and C10orf2).
317:, are known to be related to MDS.
14:
1460:Molecular Genetics and Metabolism
1246:Molecular Genetics and Metabolism
441:associated with mutations in the
80:that cause a significant drop in
2245:Diseases named after discoverers
2204:Multiple sclerosis drug pipeline
2080:Diffuse myelinoclastic sclerosis
2070:Marburg acute multiple sclerosis
2027:Diffuse myelinoclastic sclerosis
1881:Management of multiple sclerosis
1848:Radiologically isolated syndrome
1828:Expanded Disability Status Scale
345:gene, which is expressed in the
1801:Diagnosis of multiple sclerosis
978:Easton, John (19 August 2013).
2085:Tumefactive multiple sclerosis
1997:Research in multiple sclerosis
1717:Demyelinating diseases of the
931:Wheaton, Oliver (2017-07-25).
437:a form that primarily affects
381:Other causes are mutations of
1:
2230:Autosomal recessive disorders
479:associated with mutations in
289:thus move through it (called
78:autosomal recessive disorders
2164:Central pontine myelinolysis
2133:Pelizaeus–Merzbacher disease
2128:Metachromatic leukodystrophy
1823:Clinically isolated syndrome
1794:Investigations and diagnosis
1548:10.1016/j.drudis.2013.06.009
1512:10.1016/j.bbabio.2015.03.001
1355:Ostergaard E (18 May 2017).
1212:10.3109/10409238.2011.632763
799:10.1016/j.bbagen.2011.08.006
247:epilepsia partialis continua
2169:Marchiafava–Bignami disease
1472:10.1016/j.ymgme.2009.10.003
1333:(in German). Archived from
1258:10.1016/j.ymgme.2004.09.005
982:. The University of Chicago
2261:
15:
2065:Balo concentric sclerosis
873:10.1007/s13311-013-0177-6
763:10.1017/S0317167100014852
712:10.1007/s10545-015-9894-9
291:gastrointestinal motility
199:uncontrolled eye movement
54:
45:
1070:10.3389/fcvm.2021.808115
351:ribonucleotide reductase
41:mtDNA depletion syndrome
22:Myelodysplastic syndrome
1116:10.1089/dna.2004.23.797
559:Encephalomyopathic form
383:thymidine phosphorylase
245:. Seizures may include
235:intellectual disability
215:Navajo neurohepatopathy
155:), difficulty feeding,
76:, is any of a group of
2235:Mitochondrial diseases
2006:Demyelinating diseases
1719:central nervous system
1415:Liver Transplantation
1194:Copeland, WC (2012).
1028:-Related Disorders".
2108:Adrenoleukodystrophy
2032:MOG antibody disease
1834:Serological and CSF
1785:Uhthoff's phenomenon
1536:Drug Discovery Today
1104:DNA and Cell Biology
1057:Front Cardiovasc Med
960:Bernard Jacob Alpers
618:deoxyribonucleotides
421:MDDS are a group of
213:descent who develop
133:psychomotor learning
1936:Monomethyl fumarate
1331:Labor Lademannbogen
405:(for example, high
18:Mal de debarquement
2037:Multiple sclerosis
1921:Interferon beta-1b
1916:Interferon beta-1a
1911:Glatiramer acetate
1901:Diroximel fumarate
1874:Approved treatment
1727:Signs and symptoms
1661:External resources
974:Peter Huttenlocher
653:Elpeleg O (2003).
580:missense mutations
305:MDDS is caused by
241:, and progressive
100:Signs and symptoms
94:encephalomyopathic
2217:
2216:
2182:
2181:
2113:Alexander disease
1896:Dimethyl fumarate
1838:Oligoclonal bands
1806:McDonald criteria
1684:
1683:
861:Neurotherapeutics
634:Charlie Gard case
589:Hepatopathic form
423:genetic disorders
180:Charlie Gard case
176:failure to thrive
82:mitochondrial DNA
59:
58:
27:Medical condition
2252:
2010:
1980:Other treatments
1858:Dawson's fingers
1711:
1704:
1697:
1688:
1572:
1560:
1559:
1531:
1525:
1524:
1514:
1490:
1484:
1483:
1455:
1449:
1448:
1430:
1428:10.1002/lt.21556
1406:
1400:
1399:
1393:
1389:
1387:
1379:
1377:
1375:
1352:
1346:
1345:
1343:
1342:
1323:
1317:
1316:
1276:
1270:
1269:
1240:
1234:
1233:
1223:
1191:
1185:
1184:
1174:
1142:
1136:
1135:
1099:
1093:
1092:
1082:
1072:
1048:
1042:
1041:
1021:
1015:
1014:
1012:
1010:
999:
993:
991:
989:
987:
955:
949:
948:
946:
945:
928:
922:
921:
901:
895:
894:
884:
852:
811:
810:
782:
776:
775:
765:
741:
732:
731:
694:
685:
684:
674:
650:
535:physical therapy
403:laboratory tests
50:
30:
2260:
2259:
2255:
2254:
2253:
2251:
2250:
2249:
2220:
2219:
2218:
2213:
2209:Pathophysiology
2178:
2152:
2148:CAMFAK syndrome
2118:Canavan disease
2094:
2046:
2001:
1975:
1869:
1789:
1721:
1715:
1685:
1680:
1679:
1656:
1655:
1583:
1569:
1564:
1563:
1542:(19): 950–957.
1533:
1532:
1528:
1492:
1491:
1487:
1457:
1456:
1452:
1408:
1407:
1403:
1390:
1380:
1373:
1371:
1354:
1353:
1349:
1340:
1338:
1325:
1324:
1320:
1285:Nature Genetics
1278:
1277:
1273:
1242:
1241:
1237:
1193:
1192:
1188:
1144:
1143:
1139:
1110:(12): 797–806.
1101:
1100:
1096:
1050:
1049:
1045:
1023:
1022:
1018:
1008:
1006:
1001:
1000:
996:
985:
983:
977:
965:Alpers' disease
956:
952:
943:
941:
930:
929:
925:
903:
902:
898:
854:
853:
814:
784:
783:
779:
743:
742:
735:
696:
695:
688:
652:
651:
647:
642:
630:
614:
591:
561:
548:
543:
527:
419:
411:genetic testing
399:
303:
191:lactic acidosis
172:lactic acidosis
102:
74:Alper's disease
28:
25:
12:
11:
5:
2258:
2256:
2248:
2247:
2242:
2240:Rare syndromes
2237:
2232:
2222:
2221:
2215:
2214:
2212:
2211:
2206:
2201:
2196:
2190:
2188:
2184:
2183:
2180:
2179:
2177:
2176:
2171:
2166:
2160:
2158:
2154:
2153:
2151:
2150:
2145:
2140:
2135:
2130:
2125:
2123:Krabbe disease
2120:
2115:
2110:
2104:
2102:
2096:
2095:
2093:
2092:
2087:
2082:
2077:
2072:
2067:
2062:
2056:
2054:
2048:
2047:
2045:
2044:
2039:
2034:
2029:
2024:
2018:
2016:
2007:
2003:
2002:
2000:
1999:
1994:
1993:
1992:
1983:
1981:
1977:
1976:
1974:
1973:
1968:
1963:
1958:
1953:
1950:+hyaluronidase
1943:
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1928:
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1855:
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1813:Poser criteria
1810:
1809:
1808:
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1777:
1775:Optic neuritis
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1575:Classification
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1567:External links
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1931:Mitoxantrone
1765:Incontinence
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622:mitochondria
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467:
461:
455:
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431:mitochondria
420:
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358:diphosphates
347:cell nucleus
340:
338:
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328:
321:
319:
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285:
281:
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269:
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259:Hearing loss
239:quadriplegia
225:
223:
205:
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186:
184:
167:
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124:
122:
118:Motor skills
109:
107:
103:
90:hepatopathic
73:
69:
65:
61:
60:
1946:Ocrelizumab
1941:Natalizumab
1886:Alemtuzumab
1030:GeneReviews
910:GeneReviews
659:Pediatr Res
620:(dNTPs) in
157:acid reflux
38:Other names
2224:Categories
2100:Hereditary
2014:Autoimmune
1990:Daclizumab
1926:Laquinimod
1906:Fingolimod
1891:Cladribine
1865:Frexalimab
1750:Dysarthria
1740:Depression
1341:2017-04-14
1063:: 808115.
986:1 November
944:2021-09-24
640:References
295:neuropathy
163:develops.
1966:Siponimod
1961:Ponesimod
1819:Clinical
1770:Nystagmus
1755:Dysphagia
1394:ignored (
1384:cite book
541:Prognosis
525:Treatment
397:Diagnosis
307:mutations
255:blindness
149:athetosis
137:scoliosis
114:hypotonia
86:myopathic
1956:Ozanimod
1745:Diplopia
1670:Orphanet
1556:23817075
1521:25766847
1480:20074988
1445:28819842
1437:18825706
1369:20301762
1313:35417835
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1266:15639197
1230:22176657
1181:15877282
1132:20619194
1124:15684706
1089:35237671
1038:20301791
918:24741716
891:23385875
807:21855607
772:23968935
720:26475597
681:12736387
628:See also
612:Research
531:epilepsy
243:dementia
230:seizures
161:epilepsy
145:dystonia
141:kyphosis
1986:Former
1760:Fatigue
1596:: G71.3
1221:3244805
1172:1196446
1080:8882844
1009:24 July
882:3625391
728:7881205
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407:lactate
274:C10orf2
219:corneas
1735:Ataxia
1651:617156
1648:616896
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1636:615084
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301:Causes
211:Navajo
153:chorea
129:SUCLG1
125:SUCLA2
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2187:Other
2157:Other
1675:35698
1441:S2CID
1309:S2CID
1128:S2CID
976:(see
938:Metro
724:S2CID
602:MPV17
594:DGUOK
568:RRM2B
513:ECGF1
497:, or
488:MPV17
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469:RRM2B
466:, or
452:brain
447:gene;
374:DGUOK
366:mtDNA
342:RRM2B
315:FBXL4
282:ECGF1
263:liver
251:Optic
206:MPV17
187:DGUOK
168:RRM2B
92:, or
1780:Pain
1601:OMIM
1552:PMID
1517:PMID
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1476:PMID
1433:PMID
1396:help
1376:2020
1365:PMID
1301:PMID
1262:PMID
1226:PMID
1177:PMID
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1085:PMID
1034:PMID
1026:POLG
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550:The
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362:TP53
339:The
329:The
286:TYMP
270:PEO1
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1589:ICD
1544:doi
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427:DNA
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