Kuchinja kwe dopamine metabolism uye kupindura kurapwa ne levodopa/carbidopa mukushomeka kweMCT8 

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Mumushumo uyu, takaongorora mashandiro ekusagadzikana kwekufamba muAllan-Herndon-Dudley syndrome (AHDS) uye takaongorora kushanda kwelevodopa/carbidopa mukurapa. Inozivikanwawo sekushaya monocarboxylate transporter 8 (MCT8), AHDS chirwere chisingawanzoitiki cheX-linked encephalopathy chinokonzerwa nemarudzi akasiyana-siyana ezvirwere mujini reSLC16A2. Mhando dzakasiyana dzejini iri dzinokanganisa kutakurwa kwemahormone ethyroid (THs) kuburikidza neropa-uropi zvinotanga pakubata pamuviri. Izvi zvinoguma nemazinga eTH akaderera zvakanyanya mukati mehurongwa hwetsinga dzemukati uye, nekudaro, kukura kweuropi kwakachinja mumasero akawanda. 

Panyaya dzekurapa, kunze kwezviratidzo zve endocrinological, kunyanya mufananidzo we peripheral thyrotoxicosis iyo inogona kutungamira kumatambudziko akakomba e metabolic uye emwoyo, chirwere ichi chinoratidzwa nekukanganiswa kwakanyanya kwetsinga. Izvi zvinosanganisira kunonoka kukuru mukukura uye kuremara kwepfungwa, axial hypotonia, spasticity, frequent epilepsy, uye extrapyramidal signs zvinoenderana netsanangudzo ye developmental parkinsonism. 

Nekuti mahormone ethyroid akakosha pakukura kwebasal ganglia mumwana asati aberekwa uye kugadzirwa kwedopamine mushure mekusununguka, takafungidzira kuti matambudziko ekufamba anowanikwa muAHDS anobva mukukanganisika kwedopaminergic circuitry. 

Kuti tiedze fungidziro iyi, takaongorora boka revarume gumi vane matambudziko ekufamba kweropa. Chidzidzo ichi chakayera maamine emuropa mu cerebrospinal fluid (CSF) yevarwere uye takatarisa mhinduro yavo yekiriniki kuongororo ye levodopa/carbidopa kuburikidza nekuongororwa kwekiriniki, zviyero zve neuromotor functional standardized, uye kutora vhidhiyo muongororo isati yaitwa uye mushure meongororo. 

Ongororo yeCSF yakaratidza kuti pane dopaminergic pathway. Mazinga ehomovanillic acid (HVA), iyo inonzi primary dopamine metabolite, aive akaderera zvakanyanya muvarwere vatatu, nepo varwere vanomwe pavanhu gumi vakaratidza mazinga eHVA muchikamu chidiki chepakati chezera ravo. 

Mushure mezvo, vapfumbamwe vevarwere vakaongororwa levodopa/carbidopa, vachisvika padanho re10 mg/kg/zuva. Mhinduro yekiriniki yaive yakanaka zvikuru. Pamadosi anodarika 7 kusvika 8 mg/kg/zuva, vanomwe pavarwere vapfumbamwe vakaratidza kuvandudzika kwakajeka muhunhu hwavo hweparkinsonian. Kutaura zvazviri, varwere vakaratidza kudzikira kwehypokinesia nebradykinesia, pamwe nekuvandudzika kwehypomimia, zvichibvumira kutaridzika kwechiso kwakadai sekunyemwerera. Uyezve, varwere vakaratidza kutarisisa kwakawedzerwa, kudyidzana nevamwe, uye reactivity kune zvinokurudzira zvakatipoteredza. Kunyange zvazvo kuwedzera kwekushanda kwemota dzemuviri kwakakonzera action dystonia yakanyanya kuoneka mune vamwe varwere, ruzhinji rwevaya vakapindura vakaona kuvandudzika kwakazara mu gross motor function scores dzavo (GMFM-88). 

Mukupedzisa, chidzidzo ichi chinopa humbowo hwekiriniki uye hwemakemikari hunoratidza kuti kukanganiswa kwedopaminergic circuitry chikamu cheAHDS complex pathophysiology. Zvakawanikwa zvinoratidza kuti levodopa/carbidopa inzira inoshanda yekurapa kuderedza zviratidzo zvekunze kwepiramidhi uye kuvandudza reactivity yezvakatipoteredza muvarwere vane kushomeka kweMCT8. 

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