Chii ichocho? Dambudziko rekufamba-famba rinokonzerwa nekurovedza muviri mumwana mudiki
Dr. Hugo Morales Briceno: Tinokugamuchirai ku, Chii Chiripo? Nhevedzano yekukurukurirana kwenyaya itsva yekiriniki muchikamu chimwe nechimwe, nyaya chaiyo yekufamba kwechirwere, nhanho nhanho, kutanga nenhoroondo nekuongorora uye kufambira mberi kuburikidza nezviitiko, neuroimaging, zvakawanikwa murabhoritari, uye kuongororwa kwekupedzisira. Kutaura zvazviri, Chii Chiripo? inotora zita rayo kubva muchikamu chekare cheMovement Disorder Journal, chakatangwa muna 1986 naDavid Marsden naStanley Fahn senzvimbo yakaratidzwa yekutarisa kwakanyatsonaka kwekiriniki, nharo, uye kuongororwa kunotungamirirwa nezviitiko. Munhevedzano iyi, nekubatanidza hurukuro dzedu mutsananguro yakadzama yekiriniki, tinovavarira kuratidza kuti zviitiko uye syndromes zvinoramba zviri pakati pekuongororwa kunyangwe munguva yehungwaru hwekugadzira. Chinangwa pano [00:01:00] hachisi chekusvika pamhinduro nekukurumidza. Chiri pakuita kuti kufunga kwenyanzvi kuonekwe, kuti fungidziro dzinoumbwa sei, dzinogadziriswa sei, uye dzimwe nguva dzinoraswa sei sezvo ruzivo rutsva ruchibuda. Ndiri mugamuchiri wenyu Hugo Morales, uye muchikamu chino ndinofara kukurukura nyaya naProfessor Shekeeb Mohammad, chiremba wepfungwa wevana kubva kuChildren Westmead Hospital neYunivhesiti yeSydney. Shekeeb, gamuchirai.
Ona chinyorwa chakazara
Dr. Shekeeb Mohammad: Mazvita, Hugo.
Dr. Hugo Morales Briceno: Saka ndinoda kutanga nekuverenga nhoroondo yemurwere uye zvakawanikwa pakuongororwa kwetsinga dzemuviri kuvateereri vedu, uye ndozokukumbirai kuti mutsanangure zvamunoona maererano nekuongororwa kwevhidhiyo. Iye zvino uyu mukomana ane makore manomwe, akaberekwa nevabereki vasiri vemhuri imwe chete kuburikidza nekuvhiyiwa, asina zviitiko zvakakosha zvepamuviri.
Aiva nemafambiro emuviri uye kukura zvakanaka. Aiva nenhoroondo yekufamba kwegumbo zvisina kujairika kwakakonzerwa nekushanda nesimba [00:02:00] kubva pazera remakore matatu. Pakutanga, raisanganisira divi rekurudyi uye rakazopedzisira rabatanidza gumbo rekuruboshwe. Rakakonzereswa nekutamba nesimba uye kumhanya kwakasimba uye kwakagara kwemaminitsi angangoita makumi matatu.
Pakanga pasina nhoroondo yechirwere chepfari. Zvinofadza kuti munin'ina wake mudiki mukomana ane makore mashanu ekuberekwa, akaberekwa nekubvisa pfari uye aine zviitiko zvakafanana. Aivawo nezviratidzo zvakafanana nemakumbo ese ari maviri mugore rapfuura. Zviitiko zvake zvakatora nguva pfupi uye zvakapora mumaminitsi mashanu. Varwere vese vakarapwa ne levodopa pasina mhinduro, uye vabereki vake vaive vakagwinya mutsinga uye pakanga pasina nhoroondo yemhuri yechirwere chepfari. Zvino Shekeeb, ndiudzei zvamunoona muvhidhiyo, uye kana muchikwanisa kutsanangura izvozvo kuvateereri vedu.
Dr. Shekeeb Mohammad: Ndatenda neruzivo rwekiriniki. Saka ndine mavhidhiyo maviri andakapihwa. Rimwe riri pakutanga uye rimwe riri mushure mekunge mwana uyu [00:03:00] aita maekisesaizi muchimiro chekufamba kwenguva refu. Saka ndichitarisa vhidhiyo yekutanga, chandinoona mukomana mudiki ari kufamba mukamuri rekuongororwa kwekiriniki kufamba kwake kunoita sekunge kwakajairika.
Panogona kunge paine kusawirirana kudiki pakubata ruoko, asi vhidhiyo iyi idiki zvekuti handikwanise kuibvisa. Handioni mafambiro anowedzera. Handioni chimiro chakamira, uye ari kufamba netsoka dzake achirova chitsitsinho nenzira kwayo. Haasi kufamba netsoka. Saka ndiyo vhidhiyo yake yekutanga.
Uye ndinoona chitarisiko chakanaka chechiso, mafambiro emaoko akaenzana kunze kwekunge ruoko rwake rwusina kuenzana zvishoma, izvo zvandakati hatifaniri kunyanya kukoshesa tisina kumuona zvakanyanya.
Dr. Hugo Morales Briceno: Maita basa. Uye maona bvunzo yechikamu chechipiri. Pane chamunoona chakasiyana nepakutanga here?
Dr. Shekeeb Mohammad: Zvakanaka, saka ikozvino tine imwe vhidhiyo, iri mushure mekunge amanikidzwa kufamba nekusvetuka. Zvinoita sekuti kwenguva yakati, [00:04:00] hatizivi nguva chaiyo, asi chatinogona kuona pano ndechekuti kufamba kwake kwachinja zvikuru. Ari kufamba zvishoma nezvishoma zvishoma nezvishoma aine hwaro hwakamanikana uye kuenzana kwakanaka.
Asi chinhu chikuru chinoshamisa chimiro chemaoko ese pamwe chete netsoka dzake, tsoka dzake dzisina kuenzana zvishoma, dzakawanda kurudyi kuruboshwe, asi zvichienzaniswa nekuruboshwe, asi zvinoita sezviri kumativi maviri uye zvinoita sezvinosanganisirawo nhengo yepamusoro. Saka uku kuchinja uye chiitiko ichi, zvirinani pane vhidhiyo.
Zvinoita sekuti zvinomiririra chimiro chatinodaidza kuti chimiro chisina kunaka sezvo vanachiremba vachifanirwa kusimbisa izvozvo nekutarisa matauriro ake. Ndichangotarisa zvakare chitarisiko chechiso chake muvhidhiyo yechipiri iyi ndoona kana achikwanisa kuona chimwe chinhu. Ainyemwerera muvhidhiyo yekutanga.
Achiri kudaro, saka zvakare hatizopfuuri mhedziso. Dzimwe nguva pawaipa mavhidhiyo ekusagadzikana kwekufamba, unoedza kuyera zvese, kungave kunyemwerera kwe [00:05:00] kusina kunaka kana kufinyamisa chiso, asi handifungi kuti tinogona kutaura izvozvo. Asi chandingataura ndechekuti mushure mekurovedza muviri, mukomana uyu aimbove nekufamba kwakajairika iye zvino ava nekufamba kwakafanana asi kwakajairika kusina kunaka.
Uye chimiro chisina kunaka chemakumbo ekumusoro zvakare.
Dr. Hugo Morales Briceno: Mazvita, Shekeeb. Iye zvino ndichakupai rumwe ruzivo nezvekuongororwa kwake. Aive neruzivo rwakajairika sezvakataurwa muchidzidzo ichi nezvetsinga dzinogara dzichishanda. Hapana kuongororwa kwemuviri nekwepakati kwaive kusingashamisi. Kufefetera kwaivepo kwakachengetedzwa uye pakanga pasina kufefetera kwemuviri kana kusimba kwemuviri.
Chinokosha ndechekuti pakanga pasina machira eKayser-Fleischer. Zvino neruzivo urwu, unogona kungogadzira chirwere maererano nezvawakaona uye zvaunoziva nezvekuongorora?
Dr. Shekeeb Mohammad: Zvakanaka, tine nhoroondo yekare. Taona mavhidhiyo uye ikozvino tawana rumwe ruzivo. Kuti tingodzokorora, nhoroondo yake yekutanga yaifungidzirwa kuti yakajairika, uye akatanga kuita maekisesaizi ane chekuita ne [00:06:00] dystonia, yatakaona muvhidhiyo kubva pazera remakore matatu. Sekuziva kwedu, izvi hazvina kubatana nepfari kana kudzikira kwepfungwa, uye izvi zvinhu zvakakosha kuti tizive kuti sekuziva kwedu, haana matambudziko ekukura kwetsinga pakati pekunonoka kwekukura, uye haana pfari. Saka chatinosara nacho inhoroondo huru ye episodic dystonia. Uye kana ukasangana nenhoroondo iyoyo yechimwe chinhu chiri episodic kana paroxysmal, tinoedza kuona kuti chii chinobatanidzwa nezvikonzero uye nezvinhu zvinorerutsa.
Saka tinoziva kuti nekurovedza muviri, zvikamu izvi zvinouya uye ndizvo zvave zvichiitika uye ndizvo zvatakaona muvhidhiyo. Saka nehuwandu hweruzivo rwatinarwo, zvandinogona kutaura ndezvekuti izvi zvinoratidza dystonia inokonzerwa nekurovedza muviri paroxysmal mumwana ane pfungwa dzakakwana, asina nhoroondo ye [00:07:00] pfari, uye ane nhoroondo yezviitiko zvakafanana mumunun'una wake.
Dr. Hugo Morales Briceno: Ehe. Saka ikozvino tine chirwere ichi, saka paroxysmal exercise mu dystonia pamwe nekumwe kuongororwa kwakajairika uye kwetsinga, asi nenhoroondo yemhuri. Ndichakupai mimwe mhedzisiro yezviratidzo. Aive neropa rakazara rakajairika kusanganisira glucose, bvunzo dzechiropa cheitsvo, kusanganisira cerebral plasmin neammonia.
Uye aive ne lactate yakakwira kusvika pamamirigiramu makumi matatu nemana e deciliter, iyo yepamusoro iri 19 kusvika ku20. Zvakare yakaedzwa ne organic amino acid profile iyo yakanzi yaive yakajairika. Aive neCSF apo huwandu hweglucose hwaive hwakajairikawo. Zvino, nepfungwa idzi, zvino zvawava nemhedzisiro iyi pane chirwere ichi, unofunga kuti chaizoenda kupi, kana kuti ndezvipi zviratidzo pano zvinogona kukubatsira nekuongorora chirwere ichi?
Dr. Shekeeb Mohammad: Zvakare, tine [00:08:00] mamwe mashoko ekuwedzera. Ndingangotaura chimwe chinhu chandakanganwa inhoroondo isina kunaka. Saka ndinofunga kuti nguva yezuva panoitika zviitiko izvi, chero hukama nekutsanya kana kwete, zvingave zvakakoshawo munyaya iyi. Kunyanya zvinhu zvinoitika mangwanani-ngwanani.
Taizonetseka, tichifunga nezvematambudziko ekufambisa glucose, asi panguva imwe chete, zvino zvatava neruzivo rwekuti glucose yeCSF yakajairika izvo zvingaita kuti kushomeka kweglucose kutakurwa nayo kusakwanisika. Tinopiwawo huwandu hwe lactate muropa hwakakwira. Uye chimiro chidiki che acid chakajairika.
Chirwere chaWilson chinogona kutevedzera zvinhu zvakawanda, uye tinoziva kuti kusavapo kwemhete dzaKayser-Fleischer, ceruloplasmin yakajairika kungaita kuti izvi zvisave chiratidzo chetsinga dzemuviri chechirwere chaWilson. Saka pane zvimwe zvinhu zvatinofunga kuti hazvingaitiki. Panguva imwe chete, ndinofunga kuti tinofanira kudzoka toona nenhoroondo yake kuti ndeapi musiyano mukuru watiinawo.
Uye izvi zvatibatsira here kana kuti [00:09:00] hazvina kutibatsira here? Saka nenhoroondo yemukomana uyu kusvika pari zvino, uye tichitarisa vhidhiyo ine paroxysmal exercise induced disc kinesia tichifunga nezvezvikonzero zvikuru zvine chekuita nazvo zvinosanganisira kushomeka kweglucose transport.
Uye vamwe vanhu vanoonekwa vaine kushomeka kweGTP cyclohydrolase. Pamatambudziko iwayo, glucose transporter inogona kubviswa neruzivo rwatinopiwa. Kana tisina CSF monoamines, saka hatigone kubvisa kushomeka kweGTP cyclohydrolase zvichibva pane izvozvo.
Asi kusavapo kwemhinduro ye levodopa kunoratidza kuti izvozvo hazvina kunaka. Zvadaro tinosara nemamwe mapoka ezvirwere zvinogona kunge zvichikonzerwa nekuita maekisesaizi, uye akawanda acho angave aine chekuita nekuchinja kweuropi. Uye zvingatibatsira kana tikaongorora izvozvo.
Tisati tapinda mune izvozvo, zviri pachena kuti chiratidzo chacho, ropa richikwira. Pamwe zvinoratidza zvimwe zvirwere zvinosanganisira simba [00:10:00] metabolism. Zvaizova zvakavimbika zvikuru dai takaona CSF lactate yakakwira uye pamwe CSF pyruvate. Asi ndizvo zvatasara nazvo parizvino, zvekuti hatifungi kuti uku kushomeka kweglucose.
Hazvingamboiti kuti uku kushomeka kweGTP cyclohydrolase nekushaikwa kwemhinduro yelevodopa. Asi zvinogona kunge zviri zvimwe zvinhu zvinosanganisira simba remagetsi kana kuti minor acid metabolism yatingawana ruzivo kubva pakutarisa neuroimaging.
Dr. Hugo Morales Briceno: Saka ndinoona kuti wagadzira mamwe mafungiro nezve syndrome base kana kuti humbowo hwaunahwo, kusanganisira lactate, pamwe ne negative mhedzisiro kubva pabvunzo. Iye zvino ndichakupa mhedzisiro yebrain MRI, asi ndichakukumbira kuti utsanangure mhedzisiro yacho. Saka wakaongororwa brain MRI kana prevent nemunun'una wako mudiki.
Saka mungatiudze zvamunoona pano here? Kuti vateereri vedu vagone kufungidzira zviri kuitika muuropi mupfungwa dzavo here?
Dr. Shekeeb Mohammad: Ehe, saka ndakapihwa mifananidzo miviri [00:11:00]. Iyi mifananidzo ine axial T2-weighted yemukoma nemunin'ina uye axial T2-FLAIR iyo inoita kunge yeproband. Saka tichitarisa mifananidzo yeproband, tichiyeuka kuti mwana uyu ava mukupera kwemakore gumi ekutanga ehupenyu, tinogona kuona chiratidzo chakasimba kwazvo mu globi pallidi.
Uye iyi ndiyo nzvimbo inonongedzwa nemiseve. Pazera iri mukupera kwemakore gumi ekutanga, kazhinji kufambira mberi kwechiratidzo cheMRI ndekwekuti tese tinotanga kuunganidza simbi, uye kana tichienzanisa ne putamen iri pedyo, globus pallidus inofanira kuita seyakasviba. Haifanirwe kutaridzika yakajeka sezvamunoona munyaya ino.
Saka izvozvo hazvina kujairika. Zviri kutoita sezvisingaenzaniswi. Uye patinotarisa munin'ina, izvi zviri mumufananidzo we axial. Uyu mufananidzo une huremu hweT2. Uye unoona chimwe chinhu chakafanana, pamwe shanduko ye cystic pachikamu chepamberi che globi pallidi. Asi unoona symmetric [00:12:00] hyperintensities mu globus pallidus.
Saka zvakare, mukoma uyu ava nemakore mashanu ekuberekwa uye pazera iri izvi zvingave zvisina kujairika. Globus pallidus inofanira kunge yakafanana, kana isiri rima zvishoma, zvichienderana nesimba remagineti reMRI zvichienzaniswa neputamen iri pedyo.
Dr. Hugo Morales Briceno: Iye zvino tava nekukura tichiita maekisesaizi eparoxysmal mu dystonia iyi neMRI yeuropi yakajairika, ine ronda rakati mu pallidum. Nemusanganiswa uyu, ndeapi matatu ekuongorora kwako akasiyana?
Dr. Shekeeb Mohammad: Ehe. Saka izvi zvinoderedza runyorwa rwedu rwekusiyana zvakanyanya, uye kana tikabatanidza kuratidzwa kwekiriniki kwemurwere uyu neMRI, misiyano mikuru mitatu yatinosara izvirwere zvemonogenic zvinotungamira kukushomeka kwe pyruvate dehydrogenase complex. Zvirwere zvinogona kutungamira kumatambudziko mu lene, ayo ari mu minor acid metabolism uye matambudziko anogona kutungamira ku GABA [00:13:00] pathway disorders, kunyanya imwe inonzi succinic semialdehyde dehydrogenase deficiency.
Saka kana ukasanganisa zviratidzo zvekiriniki neMRI, unosara uine misiyano mikuru mitatu iyoyo.
Dr. Hugo Morales Briceno: Mazvita, Shekeeb. Zvino ndichaburitsa pachena kuongororwa kwekupedzisira kwevarwere ava. Saka zvichibva pakutevedzana kwese kwe exome, varwere vaive nemarudzi maviri ezvirwere pajini reECHS1. Iro riri mitochondrial short chain enoyl coenzyme A hydratase 1 deficiency, inova recessive disorder inogona kutungamira pakuratidzwa uku. Vabereki vemurwere uyu vakaongororwa majini. Variant yekutanga yakaonekwa muna amai, inova exon five, uye yechipiri pana baba, inova exon one. Izvi zvinosimbisa kuti nhaka ye recessive. Iye zvino ndinoda kutora mukana uyu kupa meseji yekudzokera kumba zvichibva pane zvamatsanangura kwatiri [00:14:00] Shekeeb, uye izvi zvakakosha zvishoma mu clinical phenotype, asiwo mu clinical setting paunoona varwere vachiuya kukiriniki yako.
Saka kuisa mumapoka maitiro e paroxysmal dyskinesia zvichibva pane zvinokonzera zvinogona kubatsira kugadzira runyorwa rwekuongororwa kwakasiyana uye zvikonzero. Zvakare kuvapo kwezviwanikwa zvisina kujairika zve neuroimaging kunogona kuratidza mamwe matambudziko e neurometabolic, sezvamakataura, imwe inogona kunge iri mitochondrial asi ngatisakanganwewo organic aciduria, sezvo metabolic aciduria inogonawo kuva nezviratidzo zvakafanana.
Kana muchida kuziva zvakawanda nezvenyaya iyi, nyaya iyi yakaburitswa mumagazini egore negore eIndian Academy of Neurology Journal. Musoro wayo unonzi Paroxysmal Exercise-Induced Dyskinesia in Siblings Due to ECHS1 Gene Mutation First Indian Case reports. Tinotenda zvakare nekuteerera uye ndichiripo kune inotevera, Chii Chinonzi? episode. Tinotenda zvikuru, Shekeeb.
Dr. Shekeeb Mohammad: [00:15:00] Maita basa. Maita basa nekundigamuchira.
Shekeeb Mohammad, PhD
Chipatara cheVana kuWestmead
University of Sydney
Sydney, Australia
Neurology uye Movement Disorders Unit, Westmead Hospital