Steroid responzívna encefalopatia asociovaná s autoimunitnou tyreoiditídou (SREAT) označovaná ako aj Hashimotova encefalopatia (HE) predstavuje heterogénne ochorenie s neurologickými a neuropsychiatrickými príznakmi, pri laboratórnom náleze protilátok proti štítnej žľaze a absencii inej príčiny encefalopatie. V klinickom náleze sa najčastejšie stretávame s akútnym vznikom encefalopatie pod obrazom porúch pamäti a správania, prítomnosťou epileptických záchvatov ako aj cerebelárnej alebo extrapyramídovej symptomatológie. U väčšiny pacientov pozorujeme dobrý efekt kortikoidov (metylprednisolon, prednison) s rýchlou úpravou stavu, a len malá časť pacientov vyžaduje inú imunosupresívnu terapiu (plazmaferéza, intravenózne imunoglobulíny). V práci prezentujeme prípady dvoch pacientok s akútnym rozvojom encefalopatie, status epilepticus na poklade SREAT, s úpravou stavu po kortikoidnej terapii.
Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), known as Hashimoto's encephalopathy (HE), represents a heterogeneous group of neurological and neuropsychiatric symptoms associated with a presence of antithyroid antibodies in case of other causes of encephalopathy were excluded. Clinical symptoms most commonly includes acute onset of encephalopathy, behaviour changes and cognitive dysfunction, epileptic seizures as well as cerebellar and extrapyramidal symptoms. Corticoids provides rapid and sustained therapeutic benefit in most patients and only a few patients require other immunosuppressive therapy such as plasmapheresis, intravenous immunoglobulins, or others. We present the cases of two patients with acute onset of encephalopathy, status epilepticus based on SREAT, with rapid improvement after steroid treatment.
- Klíčová slova
- steroid responzivní encefalopatie asociovaná s autoimunitní tyreoitidou,
- MeSH
- autoimunitní tyreoiditida diagnóza farmakoterapie MeSH
- diferenciální diagnóza MeSH
- glukokortikoidy aplikace a dávkování terapeutické užití MeSH
- Hashimotova nemoc * diagnostické zobrazování farmakoterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mozek diagnostické zobrazování patologie MeSH
- mozkomíšní mok chemie MeSH
- status epilepticus diagnóza MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
INTRODUCTION: Sixteen subjects with biallelic WARS2 variants encoding the tryptophanyl mitochondrial aminoacyl-tRNA synthetase, presenting with a neonatal- or infantile-onset mitochondrial disease, have been reported to date. Here we present six novel cases with WARS2-related diseases and expand the spectrum to later onset phenotypes including dopa-responsive early-onset parkinsonism and progressive myoclonus-ataxia. METHODS: Six individuals from four families underwent whole-exome sequencing within research and diagnostic settings. Following the identification of a genetic defect, in-depth phenotyping and protein expression studies were performed. RESULTS: A relatively common (gnomAD MAF = 0.0033) pathogenic p.(Trp13Gly) missense variant in WARS2 was detected in trans in all six affected individuals in combination with different pathogenic alleles (exon 2 deletion in family 1; p.(Leu100del) in family 2; p.(Gly50Asp) in family 3; and p.(Glu208*) in family 4). Two subjects presented with action tremor around age 10-12 years and developed tremor-dominant parkinsonism with prominent neuropsychiatric features later in their 20s. Two subjects presented with a progressive myoclonus-ataxia dominant phenotype. One subject presented with spasticity, choreo-dystonia, myoclonus, and speech problems. One subject presented with speech problems, ataxia, and tremor. Western blotting analyses in patient-derived fibroblasts showed a markedly decreased expression of the full-length WARS2 protein in both subjects carrying p.(Trp13Gly) and an exon-2 deletion in compound heterozygosity. CONCLUSIONS: This study expands the spectrum of the disease to later onset phenotypes of early-onset tremor-dominant parkinsonism and progressive myoclonus-ataxia phenotypes.
- MeSH
- ataxie MeSH
- dihydroxyfenylalanin MeSH
- fenotyp MeSH
- lidé MeSH
- mutace MeSH
- myoklonus * MeSH
- parkinsonské poruchy * farmakoterapie genetika MeSH
- spinocerebelární degenerace * MeSH
- tremor MeSH
- tryptofan-tRNA-ligasa * genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Lyzozómové ochorenia sú skupinou dedičných metabolických porúch spôsobených mutáciami v génoch kódujúcich rozpustné lyzozomálne hydrolázy, čo vedie k progresívnemu hromadeniu nedegradovaných makromolekúl do životne dôležitých orgánov a tkanív. Fenotypovo sú tieto poruchy charakterizované pestrým klinickým obrazom s kombináciou viscerálnych, očných, hematologických, skeletálnych a neurologických prejavov, pričom postihnutie extrapyramidového systému je obzvlášť časté. Počas posledných rokov sa dosiahol významný pokrok v liečbe týchto ochorení so zameraním na rôzne inovatívne terapeutické prístupy. Cieľom tohto prehľadu je zamerať sa na klinické rozpoznanie najčastejších lyzozómových ochorení s extrapyramídovou manifestáciou (Gaucherova choroba, Fabryho choroba a Niemann-Pickova choroba typ C, Tay-Sachsova choroba) a súčasne dostupné možnosti liečby.
Lysosomal storage disorders are a group of inherited metabolic disorders caused by mutations in genes encoding soluble lysosomal hydrolases, leading to the progressive accumulation of undegraded macromolecules in vital organs and tissues. Phenotypically, these disorders are characterised by a wide range of clinical symptoms with a combination of visceral, ocular, haematological, skeletal and neurological manifestations, with involvement of the extrapyramidal system being particularly common. Significant progress has been made in the treatment of these diseases in recent years, focusing on various innovative therapeutic approaches. The aim of this review is to focus on the clinical recognition of the most common lysosomal storage disorders with movement disorder manifestations (Gaucher disease, Niemann-Pick disease type C, Fabry disease, Tay-Sachs disease) and the current treatment options available.
- MeSH
- enzymová substituční terapie MeSH
- Fabryho nemoc patofyziologie terapie MeSH
- Gaucherova nemoc patofyziologie terapie MeSH
- lidé MeSH
- lyzozomální střádavé nemoci v nervovém systému * diagnóza terapie MeSH
- Niemannova-Pickova nemoc patofyziologie terapie MeSH
- parkinsonské poruchy terapie MeSH
- Tay-Sachsova nemoc patofyziologie terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
BACKGROUND: Despite the established value of genomic testing strategies, practice guidelines for their use do not exist in many indications. OBJECTIVES: We sought to validate a recently introduced scoring algorithm for dystonia, predicting the diagnostic utility of whole-exome sequencing (WES) based on individual phenotypic aspects (age-at-onset, body distribution, presenting comorbidity). METHODS: We prospectively enrolled a set of 209 dystonia-affected families and obtained summary scores (0-5 points) according to the algorithm. Singleton (N = 146), duo (N = 11), and trio (N = 52) WES data were generated to identify genetic diagnoses. RESULTS: Diagnostic yield was highest (51%) among individuals with a summary score of 5, corresponding to a manifestation of early-onset segmental or generalized dystonia with coexisting non-movement disorder-related neurological symptoms. Sensitivity and specificity at the previously suggested threshold for implementation of WES (3 points) was 96% and 52%, with area under the curve of 0.81. CONCLUSIONS: The algorithm is a useful predictive tool and could be integrated into dystonia routine diagnostic protocols. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.
- MeSH
- algoritmy MeSH
- dystonické poruchy * genetika MeSH
- dystonie * diagnóza genetika MeSH
- genetické testování MeSH
- lidé MeSH
- Parkinsonova nemoc * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
INTRODUCTION: Next-generation sequencing is now used on a routine basis for molecular testing but studies on copy-number variant (CNV) detection from next-generation sequencing data are underrepresented. Utilizing an existing whole-exome sequencing (WES) dataset, we sought to investigate the contribution of rare CNVs to the genetic causality of dystonia. METHODS: The CNV read-depth analysis tool ExomeDepth was applied to the exome sequences of 953 unrelated patients with dystonia (600 with isolated dystonia and 353 with combined dystonia; 33% with additional neurological involvement). We prioritized rare CNVs that affected known disease genes and/or were known to be associated with defined microdeletion/microduplication syndromes. Pathogenicity assessment of CNVs was based on recently published standards of the American College of Medical Genetics and Genomics and the Clinical Genome Resource. RESULTS: We identified pathogenic or likely pathogenic CNVs in 14 of 953 patients (1.5%). Of the 14 different CNVs, 12 were deletions and 2 were duplications, ranging in predicted size from 124bp to 17 Mb. Within the deletion intervals, BRPF1, CHD8, DJ1, EFTUD2, FGF14, GCH1, PANK2, SGCE, UBE3A, VPS16, WARS2, and WDR45 were determined as the most clinically relevant genes. The duplications involved chromosomal regions 6q21-q22 and 15q11-q13. CNV analysis increased the diagnostic yield in the total cohort from 18.4% to 19.8%, as compared to the assessment of single-nucleotide variants and small insertions and deletions alone. CONCLUSIONS: WES-based CNV analysis in dystonia is feasible, increases the diagnostic yield, and should be combined with the assessment of single-nucleotide variants and small insertions and deletions.
- MeSH
- dospělí MeSH
- dystonické poruchy diagnóza genetika MeSH
- dystonie diagnóza genetika MeSH
- kohortové studie MeSH
- lidé MeSH
- sekvenování exomu * MeSH
- variabilita počtu kopií segmentů DNA * genetika MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
DYT1 gene mutations lead to early-onset dystonia that begins with focal limb onset and spreads to other body regions within 5 years, with typical sparing of the oromandibular muscles. In the present study, we describe two patients with an unusual presentation of the disease.
- MeSH
- dítě MeSH
- dospělí MeSH
- dystonia musculorum deformans komplikace genetika patofyziologie terapie MeSH
- lidé MeSH
- tortikolis etiologie genetika patofyziologie terapie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- dopisy MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
- MeSH
- lidé MeSH
- LRRK2 genetika MeSH
- mutace MeSH
- Parkinsonova nemoc genetika MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- dopisy MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
- Maďarsko MeSH
- Polsko MeSH
- Rumunsko MeSH
- Slovenská republika MeSH
