Ukuphazamiseka Okulifa kunye Nezibonakaliso Eziphazamisayo kunye nobunzima
Isifo se-Gaucher sisifo se-genetic apho uhlobo lwe-fatty substance, eyaziwa njenge-lipid, luqala ukuqokelela kwiiseli kunye namalungu omzimba. Esi sifo sibonakala sisifo se-anemia, ukukrakra lula, amathambo amathambo, ukuphazamiseka kwemizimba, kunye nokwandiswa kwesibindi kunye nesantya.
Isifo se-Gaucher sibalwa njengengxaki yokuguqula i- autosomal disorder , oku kuthetha ukuba yimeko ezuze kubazali bomntu.
Yibangelwa ukuguqulwa kwezinto ezibizwa ngokuba yi-GBA gene apho kukho iinguqu ezingama-380 ezahlukeneyo. Ngokuxhomekeke kwiintlobo zeenguqu ezithathiwe njengelifa, abantu bangahlakulela enye yeendlela ezahlukeneyo zesifo.
Kwiintlobo ezintathu eziqhelekileyo (uhlobo 1, uhlobo lwesi-2, kunye nohlobo lwe-3), iimpawu zingaphuma kwi-mild and manageable to threatening life. Ukulinda kwexesha lokuphila kunokuchaphazeleka, ingakumbi kubantu abaneendlela ezifayo zesifo.
Isifo se-Gaucher sichaphazela ukuzalwa kwabafundi abangama-40 000 e-United States, ngokweengxelo ezivela kwi-Rockville, e-Maryland-based National Gaucher Foundation. Phantse omnye wabantu abayi-100 bakholelwa ukuba ngumphathiswa we-GBA mutation. Phakathi kwamaYuda ase-Ashkenazi, inani liphantse kwi-15 nganye.
Indlela izifo ezenza ngayo ukugula
I-GBA gene inikeza imiyalelo yokwenza uhlobo lwe-enzyme ebizwa ngokuba yi-beta-glucocerebrosidase. Le yile enzyme ejongene nokuphula uhlobo lwe lipid ebizwa ngokuba yi-glucocerebroside.
Kubantu abanesifo se-Gaucher, i-beta-glucocerebrosidase ayisekho imisebenzi njengoko kufanelekile. Ngaphandle kwendlela yokwaphula i-lipids, amazinga aqala ukuqokelela kwiiseli, ezibangela ukuvuvukala nokuphazamisa ukusebenza kweselula.
Ukuqokelela kweepilisi kumaseli e- macrophage (indima yabo iyayilahla inkunkuma yenkunkuma) ibangela ukuba bahlakulele ukubonakala kwiphepha "iphepha elinyathelisiweyo" elibizwa ngokuba yi "pathologists" njenge "Gaucher cells".
Iziganeko zesifo ziyahlukahluka ngeentlobo zeseli ezibandakanyekayo:
- Ukuqokelela i-lipids kwintolongo yesibindi, isibindi, i-pleen, imiphunga kunye nezinye izitho zingakhokelela ekunciphiseni kwamanxeba ebomvu kunye namhlophe ( pancytopenia ), isibindi esiphefumulayo kunye nesifo, nesifo sesifo somphunga.
- Ukuqokelela iiseli ze-Gaucher kwi-bone lomnxeba kunokukhokelela ekucokweni kwesakhiwo esingaphandle kwesithambo, izilonda zethambo kunye nokuxinwa kwamathambo aphantsi (i- osteopenia ).
- Ukuphazanyiswa kwamanqanaba eselunxwemeni kwesikhumba se-epidermal kunokubangela utshintsho olubonakalayo kumbala wesikhumba kunye nokuthungwa.
- Ukuqokelela kwe-lipid kwiinkqubo zesisiseko kunye neendlela zokumelana neentsholongwane kungabangela umonakalo kwisigqubuthelo esinezifo zamangqamuzana (i-myelin) kwakunye neeseli zesisindo ngokwazo.
Iintlobo zeeGaucher Disease
Izifo ze-Gaucher zihlukaniswa ngokubanzi zibe nye kwiintlobo ezintathu. Ngenxa yobubanzi obubanzi beenguqulelo ze-GBA, ubunzima kunye nesikolo sesifo sinokuhluka ngokubanzi phakathi kohlobo ngalunye. Iintlobo zichazwe njenge:
- Uhlobo lwesifo se-Gaucher 1 (eyaziwa ngokuba yi-non-neuropathic Gaucher disease) luhlobo oluqhelekileyo, lubalelwa kuma-95 ekhulwini kuwo onke amacala. Izibonakaliso zibonakala zikhulile kwaye zichaphazela kakhulu isibindi, isitha kunye nethambo. Ingqondo kunye nenkqubo yesifo ayibonakaliyo.
- Uhlobo lwesifo se-Gaucher 2 (esaziwa ngokuba sisifo esincinci se-neuropathic Gaucher disease) sichaphazela enye yezingane ezingama-100 000 ezinezibonakaliso eziqhelekileyo ziqala kwiinyanga ezintandathu zokuzalwa. Ichaphazela iinkqubo ezininzi zomzimba, kubandakanywa inkqubo ye-nervous, kwaye ngokuqhelekileyo iholele ekufeni ngaphambi kweminyaka emibini. Ngenxa yokuba abagulayo baselula kakhulu, abahlali ubomi obude ngokwaneleyo ukuphuhlisa izifo ezingekho.
- Uhlobo lwesifo se-Gaucher 3 (eyaziwa ngokuba sisifo esingapheliyo sesifo se-neuropathic Gaucher disease) senzeke kwenye yezinto zokuzalwa ezingama-100 000 kwaye singahlakulela nanini na ixesha ukususela ebuntwaneni ukuya ekubeni ngumdala. Kuqwalaselwa njengendlela ehambileyo, ehamba ngokuthe ngcembe yohlobo 2. Abantu abanomhlobo 3 bahlala behlala kwiminyaka yabo yeshumi okanye beselula.
Iimpawu
Iimpawu zesifo se-Gaucher ziyahluka kodwa ziya kuba zihlala zinezinga legazi, ukungena kwesibindi okanye ukubandakanyeka kwesibindi. Phakathi kwezinye iimpawu eziqhelekileyo:
- Ukukhathala ngenxa yokuphelelwa kwegazi
- Ukuqhwala lula ngenxa yobuninzi beplatelet count
- Isisu esisisigxina ngenxa yesibindi esivumbileyo nesantya
- Umbala wesikhumba obomvu obomvu
- Elomileyo, isikhumba esilula ( ichthyosis )
- Intlungu yesifo, intlungu edibeneyo, i-bone fractures, kunye ne- osteoporosis
Izimpawu ze-neurological ziyabonakala ngohlobo lwe-2 kwaye zihlobo lwesifo sesi-3 kodwa zenzeke ngohlobo lwe-1. Zingaquka:
- Uhlobo lwe-1: ukuqonda okungahambi kakuhle kunye nokuvakala
- Uhlobo lwe-2: ukukhwabanisa , ukuxhamla , ukunyuka kwe- apnea , nokulinda kwengqondo
- Uhlobo lwe-3: izihlunu ze-muscle, ukuxinwa, ukugula komzimba kunye nokunyuka kwamehlo
Abantu abanezifo ze-Gaucher babonakala banomngcipheko ophezulu we- myeloma (umhlaza wamaseli e-plasma kwintolongo yethambo) kunye nesifo se-Parkinson (esilunxulumene ne-GBA gene change).
Umngcipheko weGenesis
Njengaye nayiphi na ingxaki yokuxhaswa kwe-autosomal, i-Gaucher ivela xa abazali ababini bengenaso isifo ngasinye banomdla kwi- gene gene . Abazali bajongwa "ngabathwali" kuba ngamnye unomxholo ophezulu (oqhelekileyo) we-gene kunye nekopi enye ye-gene. Kuphela xa umntu ephethe ezimbini izakhi zofuzo ezinokuthi uGaucher ayenzeka.
Ukuba ngaba bobabini abazali bayithwala, umngcipheko womntwana wabo wokufumana i-Gaucher ilandelayo:
- Ipesenti ezingama-25 zithuba lokufumana iimbumba ezimbini eziphathekayo (ezichaphazelekayo)
- Ipesenti ezingama-50 zithuba elilodwa eliphambili kunye nesinye isisombululo (gene carrier)
- Ipesenti ezingama-25 zithuba lokufumana iimbumba ezimbini eziphezulu (ezingathintekiyo)
I-Genetics inokuchaza ngakumbi umngcipheko womntu wokuba nomntwana onesifo se-Gaucher. Oku kunjalo ngokukodwa kumaYuda aseAshkenazi abanomngcipheko we-Gaucher unamawaka angaphezu kwekhulu kunabantu bonke.
Iziphazamiso ze-Autosomal zichazwa ngokubanzi ngabantu abathiwa "abasunguli bomhlaba" apho isifo esizuze ilifa singabuyiselwa kwokhokho oqhelekileyo. Ngenxa yokungabikho kokuhlukahluka kofuzo kula maqela, utshintsho oluthile luye lwadluliselwa ngokulula kwimbewu, okubangelwa amazinga aphakamileyo yezifo ze-autosomal.
Ukutshintshiselwa kwamaYuda aseAshkenazi kuhambelana nohlobo lwe-2 kwaye lunokulandelwa kude emva kweMinyaka Ephakathi.
Ngokufanayo, uhlobo lwe-3 lubonakala ngokuyinhloko kubantu abavela kwingingqi yaseNorrbotten yaseSweden kwaye babuye babuyela kumsunguli oyedwa owafika enyakatho yeSweden okanye ngaphambi kwekhulu le-16.
Ukuxilongwa
Abantu abaxhonywa ukuba babe ne-Gaucher izifo baya kuhlola iimvavanyo ukujonga izinga le-beta-glucocerebrosidase egazini labo. Amanqanaba angaphantsi kwama-15 ekhulwini aqhelekileyo, kunye neempawu zekliniki, ngokuqhelekileyo ngokwaneleyo ukuqinisekisa ukuxilongwa. Ukuba kukho naluphi na ukungathandabuzeki, uvavanyo lofuzo lungasetyenziselwa ukuchonga ukuguqulwa kweGBA.
Ugqirha uza kwenza iimvavanyo ukuvavanya umonakalo amathambo, i-spleen, okanye isibindi. Oku kunokubandakanya iimvavanyo zomsebenzi wesibindi , i- absorptometry ye-X-ray absorptometry (DEXA) yokuhlola ukulinganisa ubunzima beethambo, okanye ukukhangela imifanekiso yamagnetic resonance (MRI) ukuhlola imeko yesibindi, ipeni, okanye ithambo lomongo.
Izinyango Zonyango
Ukuba umntu unesifo sohlobo lwe-Gaucher 1 okanye uhlobo lwe-3, unyango luya kubandakanya unyango lokuguqula i-enzyme (ERT). Oku kuya kubandakanywa ukuhanjiswa kwe-beta-glucocerebrosidase nge-intravenous drip.
I-US Food Management and Drug Administration (i-FDA) ivume izidakamizwa ezintathu kule ndlela:
- I-Cerezyme (i-gluccerase)
- Elelyso (taliglucerase)
- Vpriv (velaglucerase)
Ngelixa i-ERT isebenza kakuhle ekunciphiseni ubungakanani besibindi kunye neengqungquthela, ukunciphisa ukungaqhelekanga kwesifo, nokuguqula ezinye iimpawu zesifo, kubaluleke kakhulu (ngaphezulu kwama-$ 200,000 ngonyaka). Kwakungenakukwazi ukuwela umnqamlezo wengqondo , oku kuthetha ukuba kungenakusebenza ekuphatheni izifo ezinzulu ezinxulumene nengqondo.
Ngaphezu koko, ngenxa yokuba i-Gaucher isifo esingaqhathananga, akukho mntu uyaqiniseka ukuba yeyiphi imilinganiselo efunekayo ukuphumeza umphumo ophezulu ngaphandle kokugqithisa kwesi sifo.
Ngaphandle kwe-ERT, imithi emibili yomlomo iphinde ivunyiwe yi-FDA ukuvimbela ukuveliswa kwe lipids kubantu abane-type 1 Gaucher disease:
- Zavesca (miglustat)
- Cerdelga (eliglustat)
Ngokudabukisayo, akukho nonyango olululo lwe-Gaucher disease type 2. Iinjongo ziza kuba zijolise ekulawuleni iimpawu zesifo kwaye ngokuqhelekileyo zibandakanya ukusetyenziswa kwee-antibiotiki, amayeza anxamnye ne-anti-convulsive, ancedisa ukuphefumla, kunye namathambo okutya .
I-Genetic Screening
Ngenxa yokuba isifo se-Gaucher sisifo esiphezulu esisuka kubazali ukuya kwintsapho, abaninzi abantu abakwaziyo ukuba bayithwala ngenxa yokuba abanaso isifo ngokwabo.
Ukuba ungoqela elinobungozi obuphezulu okanye unenkqubela yentsapho ye-Gaucher disease, unokufuna ukuhlolwa kwezofuzo ukufumanisa isimo sakho senkonzo. Nangona kunjalo, uvavanyo lukwazi kuphela ukuchithwa kweenguqu ezisibhozo eziqhelekileyo zeGBA kwaye lunokuthi lube nemingcele kwizinto ezinokukuxelela ngengozi yakho.
Ababini abanomngcipheko owaziwayo okanye okhunjulwayo banokukhetha ukufumana iimvavanyo zofuzo ngexesha lokukhulelwa ngokukhupha iiseli ze-fetal nge-amniocentesis okanye i-chorionic villus screening (CVS). Ukuba kukho inkxalabo ye-Gaucher ephawulweyo, uvavanyo olubanzi olunzulu lunokwenziwa ukuze kuchongwe ngakumbi uhlobo.
Ukuba umphumo omuhle ubuyiselwe, kubalulekile ukuthetha nodokotela oyingcali ukuba aqonde ngokupheleleyo ukuba iyintoni intsingiselo yokuxilongwa kunye nezinto ozenzayo. Akukho zigqibo ezichanekileyo okanye ezingalunganga, kuphela eziququzelayo wena kunye neqabane lakho ninalo ilungelo lokugcina imfihlo kunye nentlonipho.
> Imithombo:
> Campbell, T. kunye noCyy, R. "Izifo ze-Gaucher kunye ne-synucleinopathies: ukucoca ubuhlobo." I-Orphanet J Rare Dis. 2012: 7:12. INGXELO: 10.1186 / 1750-1172-7-12.
> Nagral, A. "Isifo seGaucher." J Clin Exp Hepatol . 2014; 4 (1): 37 -50. INGXELO: 10.1016 / j.jceh.2014.02.005.
> I-National Gaucher Foundation. "Yintoni i-Gaucher Disease?" I-Rockville, eMaryland.
> AmaZiko eNational Health. "Isifo se-Gaucher." I-Refet Home Ref. EBethesda, eMaryn; hlaziywa ngoJanuwari 30, 2018.