Utshintsho kwi-metabolism ye-dopamine kunye nempendulo kunyango lwe-levodopa/carbidopa kwi-MCT8 deficiency 

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Kule ngxelo, siphande iindlela ezisisiseko zokuphazamiseka kwentshukumo kwi-Allan-Herndon-Dudley syndrome (AHDS) saza savavanya ukusebenza kakuhle kwe-levodopa/carbidopa. Ekwaziwa ngokuba yi-monocarboxylate transporter 8 (MCT8) deficiency, i-AHDS yi-X-linked encephalopathy engaqhelekanga kakhulu ebangelwa ziintlobo ezahlukeneyo ze-pathogenic kwi-SLC16A2 gene. Iintlobo ezahlukeneyo kule gene ziphazamisa ukuthuthwa kweehomoni ze-thyroid (THs) ngaphesheya komqobo wegazi-ingqondo ukususela ekuqaleni kokukhulelwa. Oku kuphumela kumanqanaba aphantsi kakhulu e-THs kwinkqubo yemithambo-luvo ephakathi kwaye, ngenxa yoko, kutshintshe uphuhliso lobuchopho kwiindawo ezininzi zeeseli. 

Ngokwezonyango, ngaphandle kweempawu ze-endocrine, ingakumbi umfanekiso we-peripheral thyrotoxicosis enokubangela iingxaki ezinkulu ze-metabolic kunye nentliziyo, esi sifo sibonakala ngokuphazamiseka okukhulu kwemithambo-luvo. Oku kubandakanya ukulibaziseka okukhulu kophuhliso kunye nokukhubazeka kwengqondo, i-axial hypotonia, i-spasticity, i-frequent epilepsy, kunye neempawu ze-extrapyramidal ezihambelana kakuhle nenkcazo ye-developmental parkinsonism. 

Ngenxa yokuba iihomoni ze-thyroid zibalulekile ekuphuhlisweni kwe-basal ganglia kwi-fetus kunye nokuveliswa kwe-postnatal kunye nokuthengiswa kwe-dopamine, sicinge ukuba iingxaki zokunyakaza ezibonakala kwi-AHDS zivela kukuphazamiseka kwe-dopaminergic circuitry. 

Ukuvavanya le ngcamango, sivavanye iqela lezigulane ezilishumi ezingamadoda ezibonisa iingxaki zokunyakaza ezibangelwa yi-hypokinetic. Olu phononongo lulinganise ii-amines ze-biogenic kwi-cerebrospinal fluid yezigulane (CSF) kwaye ngokujonga kwangaphambili okanye ngasemva, sijonge impendulo yazo yeklinikhi kwisilingo se-levodopa/carbidopa ngovavanyo lweklinikhi, izikali ze-neuromotor ezisebenzayo ezisemgangathweni, kunye nokurekhodwa kwevidiyo ngaphambi nasemva kwesilingo. 

Uhlalutyo lwe-CSF luqinisekisile ukubandakanyeka kwindlela ye-dopaminergic. Amanqanaba e-homovanillic acid (HVA), i-metabolite ephambili ye-dopamine, ayephantsi ngokwe-pathologically kwizigulane ezintathu, ngelixa izigulane ezisixhenxe kwezilishumi zibonise amanqanaba e-HVA kwikota ephantsi kakhulu yeminyaka yazo. 

Emva koko, izigulana ezilithoba zenze uvavanyo lwe-levodopa/carbidopa, zafikelela kwidosi ekujoliswe kuyo ye-10 mg/kg/ngosuku. Impendulo yeklinikhi yayintle kakhulu. Kwiidosi ezidlula i-7 ukuya kwi-8 mg/kg/ngosuku, izigulana ezisixhenxe kwezilithoba zibonakalise ukuphucuka okucacileyo kwiimpawu zazo ze-parkinsonian. Enyanisweni, izigulana zibonakalise ukuncipha kwe-hypokinesia kunye ne-bradykinesia, kunye nokuphucuka kwe-hypomimia, okuvumela ukubonakala kobuso okubonakalayo njengokuncuma. Ngaphezu koko, izigulana zibonise ingqalelo ephuculweyo, ukusebenzisana nabantu, kunye nokusabela kwi-environmental stimuli. Ngelixa ukwanda komsebenzi we-spontaneous motor kwabangela i-action dystonia ephawulekayo kwezinye izigulana, uninzi lwabaphenduli babone ukuphucuka ngokubanzi kwi-gross motor function scores (GMFM-88). 

Ukuqukumbela, olu phononongo lubonelela ngobungqina beklinikhi kunye ne-biochemical bokuba ukuphazamiseka kwe-dopaminergic circuitry yinxalenye ye-AHDS complex pathophysiology. Iziphumo zibonisa ukuba i-levodopa/carbidopa yindlela yonyango esebenzayo yokunciphisa iimpawu ze-extrapyramidal kunye nokuphucula ukusabela kwendalo kwizigulana ezinengxaki yokungabikho kwe-MCT8. 

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