Amyotrophy, cerebellar impairment and psychiatric disease are the main symptoms in a cohort of 14 Czech patients with the late-onset form of Tay-Sachs disease

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F19%3A10395741" target="_blank" >RIV/00064165:_____/19:10395741 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/19:10395741 RIV/00216208:11130/19:10395741 RIV/00064203:_____/19:10395741

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=cV60WgAlzg" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=cV60WgAlzg</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00415-019-09364-3" target="_blank" >10.1007/s00415-019-09364-3</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Amyotrophy, cerebellar impairment and psychiatric disease are the main symptoms in a cohort of 14 Czech patients with the late-onset form of Tay-Sachs disease

Popis výsledku v původním jazyce

Background Tay-Sachs disease (TSD) is an inherited neurodegenerative disorder caused by a lysosomal beta-hexosaminidase A deficiency due to mutations in the HEXA gene. The late-onset form of disease (LOTS) is considered rare, and only a limited number of cases have been reported. The clinical course of LOTS differs substantially from classic infantile TSD. Methods Comprehensive data from 14 Czech patients with LOTS were collated, including results of enzyme assays and genetic analyses. Results 14 patients (9 females, 5 males) with LOTS were diagnosed between 2002 and 2018 in the Czech Republic (a calculated birth prevalence of 1 per 325,175 live births). The median age of first symptoms was 21 years (range 10-33 years), and the median diagnostic delay was 10.5 years (range 0-29 years). The main clinical symptoms at the time of manifestation were stammering or slurred speech, proximal weakness of the lower extremities due to anterior horn cell neuronopathy, signs of neo- and paleocerebellar dysfunction and/or psychiatric disorders. Cerebellar atrophy detected through brain MRI was a common finding. Residual enzyme activity was 1.8-4.1% of controls. All patients carried the typical LOTS-associated c.805G&gt;A (p.Gly269Ser) mutation on at least one allele, while a novel point mutation, c.754C&gt;T (p.Arg252Cys) was found in two siblings. Conclusion LOTS seems to be an underdiagnosed cause of progressive distal motor neuron disease, with variably expressed cerebellar impairment and psychiatric symptomatology in our group of adolescent and adult patients. The enzyme assay of beta-hexosaminidase A in serum/plasma is a rapid and reliable tool to verify clinical suspicions.

Název v anglickém jazyce

Amyotrophy, cerebellar impairment and psychiatric disease are the main symptoms in a cohort of 14 Czech patients with the late-onset form of Tay-Sachs disease

Popis výsledku anglicky

Background Tay-Sachs disease (TSD) is an inherited neurodegenerative disorder caused by a lysosomal beta-hexosaminidase A deficiency due to mutations in the HEXA gene. The late-onset form of disease (LOTS) is considered rare, and only a limited number of cases have been reported. The clinical course of LOTS differs substantially from classic infantile TSD. Methods Comprehensive data from 14 Czech patients with LOTS were collated, including results of enzyme assays and genetic analyses. Results 14 patients (9 females, 5 males) with LOTS were diagnosed between 2002 and 2018 in the Czech Republic (a calculated birth prevalence of 1 per 325,175 live births). The median age of first symptoms was 21 years (range 10-33 years), and the median diagnostic delay was 10.5 years (range 0-29 years). The main clinical symptoms at the time of manifestation were stammering or slurred speech, proximal weakness of the lower extremities due to anterior horn cell neuronopathy, signs of neo- and paleocerebellar dysfunction and/or psychiatric disorders. Cerebellar atrophy detected through brain MRI was a common finding. Residual enzyme activity was 1.8-4.1% of controls. All patients carried the typical LOTS-associated c.805G&gt;A (p.Gly269Ser) mutation on at least one allele, while a novel point mutation, c.754C&gt;T (p.Arg252Cys) was found in two siblings. Conclusion LOTS seems to be an underdiagnosed cause of progressive distal motor neuron disease, with variably expressed cerebellar impairment and psychiatric symptomatology in our group of adolescent and adult patients. The enzyme assay of beta-hexosaminidase A in serum/plasma is a rapid and reliable tool to verify clinical suspicions.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Neurology

ISSN

0340-5354

e-ISSN

—

Svazek periodika

266

Číslo periodika v rámci svazku

8

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

7

Strana od-do

1953-1959

Kód UT WoS článku

000476506500015

EID výsledku v databázi Scopus

2-s2.0-85065702504