Myotonia lihaksen ionikanavataudeissa

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Lapsuuden mitokondriotaudit - yhden soluelimen toimintaviasta kymmeniä erilaisia sairauksia

Vertaisarvioitu. English abstract.Lapsuudessa alkavat mitokondriotaudit ovat useimmiten eteneviä aivo- tai lihastauteja, joihin voi liittyä muiden elimien, kuten maksan, sydämen, munuaisten ja aistinelinten toiminnanhäiriöitä. Mitokondriotaudit ovat yksi yleisimmistä periytyvistä aineenvaihduntatautiryhmistä, ja niiden mahdollisuus tulisi pitää mielessä, kun lapsella on tunnistamaton, etenevä sairaus. Diagnosointi on vaativaa kliinisen kuvan monimuotoisuuden, laboratoriotutkimusten epäspesifisyyden ja joidenkin tarkennettujen tutkimusten, kuten lapsilta nukutuksessa otettavan lihaskudosnäytteen, kajoavan luonteen vuoksi. Uudet genominlaajuiset tutkimusmenetelmät ovat osoittautuneet arvokkaiksi lasten mitokondriotautien diagnostiikassa. Vain yksittäisiin mitokondriotauteihin on toistaiseksi täsmähoitoja. Kaikki potilaat tarvitsevat kuitenkin yksilöllistä hoitoa, kuntoutusta ja pysyviä hoitosuhteita, perheet puolestaan sekä perinnöllisyysneuvontaa että pitkäjänteistä tukea.Peer reviewe

Veltto imeväinen

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Motoneuronitautien lääkehoito - uutuuksia näköpiirissä

Vertaisarvioitu.Motoneuronitaudit ovat ryhmä harvinaisia tauteja, jotka johtavat usein kuolemaan ja joihin on toistaiseksi ollut tarjolla vain oireenmukaista hoitoa. Geenivirheiden osuus näiden tautien etiologiassa vaihtelee tuntemattomasta myötävaikuttavan kautta täydelliseen. Karttuva tieto sairauksien ja niille altistavien tekijöiden geneettisestä taustasta on mahdollistanut täsmälääketieteen esiinmarssin eli lisännyt räätälöityjen hoitojen tarjontaa. Yhtenä ongelmana on kustannus-hyötysuhde, koska uudet hoidot ovat kalliita. Esittelemme yleisimpien motoneuronitautien, amyotrofisen lateraaliskleroosin (ALS) ja spinaalisen lihasatrofian (SMA) hoitojen nykytilaa ja lähitulevaisuuden näkymiä.Peer reviewe

Reply to 'Letter to Editor by Finsterer J and Zarrouk-Mahjoub S : Phenotypic manifestations of the m.8969G > A variant'

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Cost-effectiveness of whole-exome sequencing in progressive neurological disorders of children

Objectives: To clarify the diagnostic utility and the cost-effectiveness of whole-exome sequencing (WES) as a routine early-diagnostic tool in children with progressive neurological disorders. Methods: Patients with infantile-onset severe neurological diseases or childhood-onset progressive neurological disorders were prospectively recruited to this WES study, in the pediatric neurology clinic at Helsinki University Hospital during 2016-2018. A total of 48 patients underwent a singleton WES. A control group of 49 children underwent traditional diagnostic examinations and were retrospectively collected from the hospital records. Their use of health care services, related to the diagnostic process, was gathered. Incremental cost-effectiveness ratio (ICER) per additional diagnosis was calculated from the health care provider perspective. Bootstrapping methods were used to estimate the uncertainty of cost-effectiveness outcomes. Results: WES provided a better diagnostic yield (38%) than diagnostic pathway that did not prioritize WES in early diagnosis (25%). WES outperformed other diagnostic paths especially when made early, within one year of first admission (44%). Cost-effectiveness in our results are conservative, affected by WES costs during 2016-18. Conclusions: WES is an efficient and cost-effective diagnostic tool that should be prioritized in early diagnostic path of children with progressive neurological disorders. The progressively decreasing price of the test improves cost-effectiveness further. (C) 2021 The Authors. Published by Elsevier Ltd on behalf of European Paediatric Neurology Society.Peer reviewe

Using urine to diagnose large-scale mtDNA deletions in adult patients

Objective: The aim of this study was to evaluate if urinary sediment cells offered a robust alternative to muscle biopsy for the diagnosis of single mtDNA deletions. Methods: Eleven adult patients with progressive external ophthalmoplegia and a known single mtDNA deletion were investigated. Urinary sediment cells were used to isolate DNA, which was then subjected to long-range polymerase chain reaction. Where available, the patient's muscle DNA was studied in parallel. Breakpoint and thus deletion size were identified using both Sanger sequencing and next generation sequencing. The level of heteroplasmy was determined using quantitative polymerase chain reaction. Results: We identified the deletion in urine in 9 of 11 cases giving a sensitivity of 80%. Breakpoints and deletion size were readily detectable in DNA extracted from urine. Mean heteroplasmy level in urine was 38% +/- 26 (range 8 - 84%), and 57% +/- 28 (range 12 - 94%) in muscle. While the heteroplasmy level in urinary sediment cells differed from that in muscle, we did find a statistically significant correlation between these two levels (R = 0.714, P = 0.031(Pearson correlation)). Interpretation: Our findings suggest that urine can be used to screen patients suspected clinically of having a single mtDNA deletion. Based on our data, the use of urine could considerably reduce the need for muscle biopsy in this patient group.Peer reviewe

Attitudes towards genetic testing and information : does parenthood shape the views?

This study examines how parents of pediatric patients might differ in their views and attitudes towards genetic technology and information when compared to adult patients. There is surprisingly little evidence on how parents compare to other parts of population in their attitudes. Previous empirical studies often relate health-related preferences and attitudes to factors such as age, education, and income instead of parental status, thus evading comparison of parents to others as health-related decision makers. Findings related to the parental status can be useful when implementing genetic technology in clinical practice. We conducted a survey of views on genetic technology and information for groups of adult neurology patients (n = 68) and parents of pediatric neurology patients (n = 31) to shed some light on this issue. In addition to our own survey instrument, we conducted other surveys to gain insight on psychosocial factors that might affect these attitudes. The results suggest that parents are more concerned about their children's genetic risk factors when compared to the attitudes of adult patients about their own risk. For both groups, negative emotional state was associated with more concerns towards genetic information. Our study provides insights on how parental views might affect the acceptance of genetic technology and information.Peer reviewe