
methylmalonic acidemia

methyl malonic aciduria anie kooda piluvabade methyl malonic acidemia anedi saadhaarana amaino aamlam jeevakriyaku antaraayam kaliginche autosomal recessive metabolic desorder. idhi sendriya aamleeyata yokka shaastreeya rakam. eee paristhiti phalitamgaa nirdishta kovvulu mariyu proteinlanu sarigga jeernam cheyalekapovadam, idhi raktamlo methyl malonic aamlam yokka visha sthaayini penchadaaniki daariteestundi.
methylmalonic acidemia aneka janyuroopaala nundi udbhavistundi, anni rakaala rugmatalu saadhaaranamgaa prarambha navjata kaalamlo nirdhaarana cheyabadataayi, pragatiseela encephalopathy mariyu dviteeya hypermonemia pradarsistaayi. vyaadhi nirdhaarana cheyakapothe ledhaa chikitsa cheyakunda vadilesthe eee rugmata maranaaniki daariteeyavachchu. eee rugmata 48,000 jananaalalo 1 yokka frequencini kaligi untundani anchanaa veyabadindi, ayithe rooga nirdhaarana kesulalo adhika maranaala raetu khachitamaina nirdhaarananu kashtataram chestundi. methyl malonic acidemias jaathi sarihaddula meedugaa samaana pounahpunyamtho kanipistaayi.
lakshanaalu mariyu sankethaalu.
prabhaavita janyuvulanu batti, eee rugmata telikapati nundi praanaantakamaina lakshanaalanu pradarsinchavacchu.
kaaranam.
janyu.
methyl malonic acidemia yokka vaarasatvamgaa vacchina roopaalu jeevakriya maargamlo lopaalanu kaligistaayi, ikkada methyl malonil-kmjime eah (koe) nuu methyl malonil-koo mutase enjaim dwara sasinail-koga maarchabadutundi.
methyl malonyl-koaanu sasinail-koaga maarchadaaniki kooda vitamin bii12 avasaram. vitamin bii12 gvakriyalo lopalaku ledhaa daani ravaanaalo lopalaku daariteese utparivartanalu tarachugaa methylmalonic acidemia abhivruddhiki daariteestaayi.
eee rugmata autosomal recessive inheritance namuunaanu kaligi untundi, antey lopabhuishta janyuvu autosompy undhi, mariyu janyuvu yokka rendu kaapeelu-prati parent nundi okati-rugmata dwara prabhaavitamavadaaniki vaarasatvamgaa ravali. autosomal recessive desorder unna pillala tallidandrulu lopabhuishta janyuvu yokka oka kaapeeni kaligi untaaru, conny saadhaaranamgaa eee rugmata dwara prabhaavitam kaadu.
poeshakaahaaram.
ellappuduu vaarasatvamgaa vacchina samskaranalatho kalisi samuuham cheyabadanappatiki, vitamin bii12 yokka teevramaina poeshaka lopam kooda janyu methylmalonic acidemias maadirigaane lakshanaalu mariyu chikitsalatho syndromeku daariteestundi. methylmalonyl-koaaku sasinail-koaa erpadataaniki vitamin bii12 avasaram. cofactor methyl malonil-koaanu sasinail-koaga maarchadaaniki bii12 parimaanam sariponippudu, upayoginchani methyl malonil-koaa nirmaanam chivariki methyl malonic acidemiaku daariteestundi. eee roganirdhaarana tarachugaa seeram loe vitamin bii12 lopaniki suuchikagaa upayoginchabadutundi.
yantraangam.
pathophysiology.
methyl malonic acidemialo, sareeram amaino aamlalu methionin, thrionin, isolucin mariyu vaalinlanu vichchinnam cheyalekapoyindi; phalitamgaa raktamlo mariyu kanajaalaalo methyl malonic aamlam erpadutundi. eee rugmatato badhapaduthunna vaariki kriyaatmaka kaapeelu ledhaa krindi okati ledhaa anthakante ekkuva enjaimla taginanta sthaayilu undavuh methylmalonil-cova mutase, methylmalonil-cova epimerase ledhaa adenosyl cobalamine samshlaeshanhaloo palgonevi.
methylmalonyl-cova mutage.
60 saatam kesulu protein methylmalonil-cova mutaysnu encode chese utparivartana chendina "mute" janyuvu phalitamgaa unnayani anchanaa. paina perkonna amaino aamlalu mariyu kovvula vichchinnam yokka vishapuurita utpannaala jeernakriyaku eee enjaim baadhyata vahistundi, pradhanamgaa collustroll, mukhyamgaa eee enjaim methyl malonil-kovanu sasinail-koga maarustundi. eee enjaim lekunda, sariiraaniki methylmalonic aamlam mariyu sambandhita sammelanaalanu thatastheekarinchadaaniki ledhaa tolaginchadaaniki maargam ledhu. eee enjaim yokka charyanu "emma", "mmab" mariyu "mmhc" janyuvulalo utparivartana dwara kooda angavaikalyam cheyavachu, veetilo prati okkati methylmalonil-cova mutase yokka saadhaarana paniteeruku avasaramaina proteinnu encode chestundi.
methylmalonil-cova epimerase.
methylmalonil-cova epimerase proteinnu encode chese "mussy" janyuvulooni utparivartanalu, dheenini methylmalonil racemase anie kooda pilustaaru, idhi sambandhita methylmalonil-cova mutase roopaantaram kante rugmata yokka chaalaa telikapati roopaanni kaligistundi. mutage maadirigaane, epimerase kooda adhe padaarthaalanu vichchinnam cheyadamlo panichestundi, conny mutase kante gananeeyamgaa takkuva sthaayilo panichestundi. mutaseku viruddhamgaa epimerase lopam valla kalige samalakshana vyatyaasaalu chaalaa telikapativi, eee janyu lopaanni rugmata ledhaa clinical syndromga pariganinchavacchaa ledhaa anae daanipai vaidya samaajamlo charcha jarugutondi.
adenosyl cobalamine.
vitamin bii12 anie kooda piluvabade cobalamine yokka eee roopam methylmalonil-cova mutage yokka avasaramaina cofactor. saareerakamgaa saadhaarana sthaayilalo enjaim yokka kriyaatmaka samskaranatho kooda, bii12naaii eee kriyaaseela roopaaniki marchalekapothe, mutage panicheyadu.
purogati.
vyaadhi yokka pratyeka dasalu laenappatikee, methyl malonic acidemia anedi oka pragatiseela paristhiti; methyl malonic aamlam yokka gaadata perige koddi eee rugmata yokka lakshanaalu militam avtayi. aahaaramlo prerepinche proteins mariyu kovvulanu tholaginchakapothe, eee perugudala kolukoleni moothrapindaalu ledhaa kaaleya nashtaniki mariyu chivariki maranaaniki daariteestundi.
rooga nirdhaarana.
vaatilo okati, sendriya aamleeyata yokka atyanta saadhaarana roopam kakapoyina, methylmalonic aamleeyata puttukathone spashtamgaa kanipinchadu, endukante sisuvu aahaaramlo proteinlanu jodinche varaku lakshanaalu saadhaaranamgaa kanipinchavu. eee kaaranamgaa, lakshanaalu saadhaaranamgaa jeevitam yokka modati samvatsaramlo eppudaina kanipistaayi. eee rugmata nirdhaarana cheyabadakapothe sanklishtatalanu kaliginche teevrata mariyu vegamu kaaranamgaa, methylmalonic acidemia kosam screening tarachugaa navjata screening pareekshalo cherchabadutundi.
amaino aamlaalanu puurtigaa vichchinnam cheyalekapovadam valla, protein jeernakriya yokka upa utpatti, methylmalonic aamlam anae sammelanam, badhapaduthunna vaari raktam mariyu moothramlo asamaana saandrataloo kanipistundi. eee asaadhaarana sthaayilu rugmata nirdhaaranaku pradhana roganirdhaarana pramanaluga upayoginchabadataayi. eee rugmata saadhaaranamgaa moothra vislaeshanha ledhaa rakta phalakam upayoginchadam dwara nirnayinchabadutundi. siti ledhaa mri skaan ledhaa ammonia pareekshanu upayoginchadam dwara kooda methylmalonic acidemia unikini anumaaninchavacchu, ayithe eee pareekshalu yea vidhamgaanuu nirdishtamainavi kaavu mariyu clinical mariyu jeevakriya/sahasambandham avasaram. raktam mariyu moothramlo ammonia, glycine mariyu keaton sareeraala yokka adhika sthaayilu kooda undavacchu.
rakalu.
methylmalonic acidemialo vividha rooga nirdhaaranalu, chikitsa avasaralu mariyu rooga niroopanalu unnaayi, ivi rugmata yokka vaarasatvamgaa vacchina roopaaniki kaaranamayye nirdishta janyu utparivartana dwara nirnayinchabadataayi. methyl malonic acidemiaku kaaranamayye janyuroopaalu eee krindi vidhamgaa unnaih
mute rakanni mute0 mariyu mute-upa rakaluga vibhajinchavachhu, mute0 methyl malonil-cova mutage yokka puurti lekapovadam mariyu marinta teevramaina lakshanaalu mariyu mute-mutage charya yokka taggina mottam dwara vargeekarinchabadutundi.
methylmalonic acidemia yokka mute-, sii. bii. ell. bii mariyu sii. bii. ell. eah. versionlu cobalamine pratispandinchevigaa kanugonabaddayi. mute0 anedi pratispandinchani roopaantaram.
chikitsa.
aahara.
eee paristhiti yokka anni rakaala chikitsa pradhanamgaa takkuva protein aaharam meeda aadharapadi untundi, mariyu vyakti yea rakamaina rugmatato badhapaduthunnado, vividha aahara padaardhaalapai aadharapadi untundi. anni rakalu carnitine yokka levo isomercu pratispandistaayi, endukante prabhaavita padaarthaala akrama vichchinnam valla baadhitulu carnitine lopaanni abhivruddhi chestaaru. carnitine asil-cova tolagimpuloo kooda sahaayapadutundi, idhi takkuva protein aaharalalo moothramlo visarjinchagala asil-carnitinega marchadam dwara saadhaaranam. konni rakaala methylmalonyl acidemia kobalaminku pratispandistaayi, ayithe sinocobalamine supplements konni roopaalaku hanikaram anie niroopinchavacchu. vyakti cobalamine mariyu carnitine supplementlaku pratispandistundani rujuvu chesthe, appudu vaaru samasyaatmaka amaino aamlalu isolucin, thrionin, methionin mariyu valin vanti chinna mottamlo unde padaarthaalanu daadi cheyakunda teesukune avakaasam untundi.
shastra chikitsa.
marinta teevramaina chikitsalo eee paristhiti lekunda daata nundi moothrapindaalu ledhaa kaaleya marpidi untundi. bahya avayavalu lopabhuishta enjaimla kriyaatmaka samskarananu utpatti chestaayi mariyu methylmalonic aamlanni jeernam chestaayi, ayithe avayava marpidi yokka anni pratikuulatalu eee paristhitiloo vartistaayi. kendra naadii vyavastha sariiramlooni migilina bhagala nundi verucheyabadina vyavasthalo methylmalonil-cova jeevakriyanu cheyagaladani suuchimchadaaniki aadharalu unnaayi. idhe jarigithe, maarpidiki mundu methylmalonic aamlam yokka naraala prabhavalanu marpidi cheyakapovachhu ledhaa nirantaram peragadam dwara medaduku marinta nashtam jaragakunda nirodhinchavacchu.
rooga niruupana.
paristhiti yokka teevrata mariyu chikitsaku vyakti yokka pratispandananu batti rooga niruupana maarutundi. cobalamine-pratispandinche vaividhyaalu unnavaariki rooga niruupana saadhaaranamgaa manchidi mariyu cobalamine-pratispandinchani vaividhyaalatoe badhapaduthunna vaarilo asajanakamga undadu. telikapati vaividhyaalu marinta teevramaina vaati kante janabhalo ekkuva tarachugaa kanipistaayi. aahaaramlo maarpu mariyu nirantara vaidya samrakshanhatho kooda, pratispandinchani acidemia unnavaarilo naraala sambandhita nashtanni nivaarinchadam saadhyam kakapovachhu. saraina chikitsa ledhaa rooga nirdhaarana lekunda, modati aamla daadi praanaantakam kavadam asaadhaaranam kaadu.
eee savaallu unnappatikee, 1967loe dheenini modatisaarigaa gurtinchinappati nundi, chikitsa mariyu paristhiti gurinchi avagahana anedi methylmalonic acidemia yokka pratispandinchani roopaalu unnavaaru kooda yuktavayassuku cherukogalaru mariyu pillalanu surakshitamgaa mosukelli prasavinchagalaru anie vinani sthaayiki merugupadindi.
parisoedhana.
nosologic charitra.
mma modata oberholzer mariyu itarulu kaligi unnaaru. 1967loe.
naraala prabhavalu.
mma naadii vyavasthapai vinaasakaramaina prabhavalanu chuupagaladani chaalaa kaalamgaa nivedinchabadindi; ayithe, idhi sambhavinche vidhanam ennadoo nirnayinchabadaledu. juun 15,2015naa prachurinchabadina, inn vitro settinglo pindam elukala nundi verucheyabadina neuranlapy methylmalonic aamlam yokka prabhavalapai nirvahinchina parisoedhana, idhe vidhamaina pihech yokka pratyaamnaaya aamlamtho chikitsa cheyabadina neuronla niyantrana samuuhaanni upayogistundi. methyl malonic aamlam cellular parimaanamlo taggudalaku kaaranamavutundani mariyu adhika saandratala vadda marinta teevramaina prabhavalanu chudadamto yekagratapai aadhaarapadina paddhatiloo cellular apoptosis retulo perugudalaku kaaranamavutundani eee pareekshalu suuchimchaayi. inca, eee chikitsa cheyabadina neuronla suukshma shreni vislaeshanha kooda epigenetic-sthaayi methylmalonic aamlam 564 janyuvula transcription retunu maarustundani suuchimchimdi, mukhyamgaa apoptosis, pii53 mariyu mapk signalling margalalo palgonna vaatitho sahaa.
mitochondrial panicheyakapovadam.
methyl malonyl-cova nuu sasinail-cova gaa marchadam mitochondria lopala jarugutundi kabatti, electron ravana golusu paniteeru taggadam phalitamgaa mitochondrial panicheyakapovadam anedi mmlo oka lakshanamgaa chalakalamga anumaaninchabadindi. iteevali parisoedhanaloo eluka namoonaalalo eee rugmatato prabhaavitamaina elukala mitochondria asaadhaarana parimaanaaniki perugutundani kanugonnaru, dheenini megametochandria anie pilustaaru. eee megametochandria kooda antargata nirmaanaalanu vaikalyam chesi, vaati antargata maatrukalo electron samruddhini kolpoyi unnatlu kanipistundi. eee megametochandria kooda swaasakosha golusu paniteeru taggina sankethaalanu choopinchindi, mukhyamgaa swaasakosha sanklishtata IV loe idhi kevalam 50 saatam saamardhyamtho matrame panichesindi. mmatho badhapaduthunna 5 yella baludi nundi marpidi samayamlo tolaginchina kaaleya namuunaa yokka mitochondrialo ilanti maarpulu gurtinchabaddaayi.
nirapaayamaina mute samalakshanam.
pii anie piluvabade nirdishta mutationtho pratispandinchani mute0 mmnu pradarsinche aneka mandhi rogulalo iteevali cases studies.mute rakam mmalo marinta upavibhaagam unde avakaasam undani p86l suuchistunnaayi. cobalamine supplementlaku puurti pratispandana laenappatikee, idhi nirdishta mutation ledhaa mundastu gurtimpu mariyu chikitsa kaaranamgaa jariginda anedi prastutam aspashtamgaa unnappatikee, eee vyaktulu ekkuvagaa nirapaayamaina mariyu daadaapu puurtigaa lakshanarahitamaina mma versionnu abhivruddhi chesinatlu kanipinchaaru. raktam mariyu moothramlo sthiramgaa perigina methyl malonic aamlam kanipinchinappatikii, eee vyaktulu chaalaa varaku abhivruddhi chendutuu saadhaarana sthithilo kanipinchaaru.