Biallelic variants in the NARS2 gene are the cause of a continuous spectrum of neurodegenerative disorders presenting with various severity-from spastic paraplegia, progressive neurodegeneration to Leigh and Alpers syndrome. Common clinical signs result from a mitochondrial dysfunction based on OXPHOS deficiency. Here, we present a patient with infantile-onset severe epilepsy leading to fatal refractory status epilepticus. Whole exome sequencing with Exomiser analysis based on HPO terms detected two novel NARS2 variants in a compound heterozygous state. To date, 18 different NARS2 disease-causing mutations have been described. Our study adds to the understanding of this mitochondrial disorder.
- MeSH
- aspartát-tRNA-ligasa genetika MeSH
- epilepsie diagnóza genetika MeSH
- lidé MeSH
- mitochondriální nemoci genetika MeSH
- mutace genetika MeSH
- novorozenec MeSH
- věk při počátku nemoci MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Recently, biallelic variants in the SORD gene were identified as causal for axonal hereditary neuropathy (HN). We ascertained the spectrum and frequency of SORD variants among a large cohort of Czech patients with unknown cause of HN. Exome sequencing data were analysed for SORD (58 patients). The prevalent c.757del variant was tested with fragment analysis (931 patients). Sanger sequencing in additional 70 patients was done. PCR primers were designed to amplify the SORD gene with the exclusion of the pseudogene SORD2P. Sequence differences between gene and pseudogene were identified and frequencies of SNPs were calculated. Eighteen patients from 16 unrelated families with biallelic variants in the SORD gene were found and the c.757del was present in all patients on at least one allele. Three novel, probably pathogenic, variants were detected, always in a heterozygous state in combination with the c.757del on the second allele. Patients presented with a slowly progressive axonal HN. Almost all patients had moderate pes cavus deformity. SORD neuropathy is frequent in Czech patients and the third most common cause of autosomal recessive HN. The c.757del is highly prevalent. Specific amplification of the SORD gene with the exclusion of the pseudogene is essential for a precise molecular diagnostics.
- MeSH
- dospělí MeSH
- hereditární motorické a senzitivní neuropatie * diagnóza epidemiologie genetika MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mutace MeSH
- sekvenování exomu MeSH
- senioři MeSH
- sorbitoldehydrogenasa genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
- Publikační typ
- abstrakt z konference MeSH
The objectives of this study were to evaluate patients with aortic abdominal aneurysm (AAA) with regard to immunoglobulin (Ig)G4-related disease (IgG4-RD). IgG4-RD represents a recently defined condition comprised of a collection of disorders characterized by IgG4 hypergammaglobulinemia, the presence of IgG4-positive plasma cells in organs affected with fibrotic or sclerotizing changes and typical histopathological features. It was identified as a possible cause of vasculitis in large vessels. Studies have been published on a possible association between inflammatory aortic or cardiovascular disease and IgG4-RD. We examined 114 patients with AAA requiring surgery in order to identify findings which are characteristic of IgG4-RD. Aneurysm samples from seven patients showed histopathological features consistent with IgG4-RD and the presence of IgG4+ plasma cells. Only two of these seven patients showed elevated IgG4 serum levels higher 1·35 g/l. In five of the patients, the concentration of serum IgG4 was lower than 1·20 g/l, with the number of IgG4+ plasma cells being higher than 50/high-power field. These findings were consistent with AAA being a heterogeneous group of inflammatory diseases with different pathogenesis.
- MeSH
- aneurysma břišní aorty krev imunologie patologie MeSH
- aorta imunologie metabolismus patologie MeSH
- hypergamaglobulinemie krev imunologie patologie MeSH
- IgG4 asociovaná nemoc krev imunologie patologie MeSH
- imunoglobulin G krev imunologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- plazmatické buňky imunologie metabolismus patologie MeSH
- retrospektivní studie MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- práce podpořená grantem MeSH
Biallelic SBF2 mutations cause Charcot-Marie-Tooth disease type 4B2 (CMT4B2), a sensorimotor neuropathy with autosomal recessive inheritance and association with glaucoma. Since the discovery of the gene mutation, only few additional patients have been reported. We identified seven CMT4B2 families with nine different SBF2 mutations. Revisiting genetic and clinical data from our cohort and the literature, SBF2 variants were private mutations, including exon-deletion and de novo variants. The neuropathy typically started in the first decade after normal early motor development, was predominantly motor and had a rather moderate course. Electrophysiology and nerve biopsies indicated demyelination and excess myelin outfoldings constituted a characteristic feature. While neuropathy was >90% penetrant at age 10 years, glaucoma was absent in ~40% of cases but sometimes developed with age. Consequently, SBF2 mutation analysis should not be restricted to individuals with coincident neuropathy and glaucoma, and CMT4B2 patients without glaucoma should be followed for increased intraocular pressure. The presence of exon-deletion and de novo mutations demands comprehensive mutation scanning and family studies to ensure appropriate diagnostic approaches and genetic counseling.
- MeSH
- biopsie MeSH
- Charcotova-Marieova-Toothova nemoc diagnóza genetika MeSH
- dítě MeSH
- dospělí MeSH
- fenotyp * MeSH
- genetická predispozice k nemoci * MeSH
- genetické asociační studie * metody MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mutace * MeSH
- nereceptorové tyrosinfosfatasy genetika MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
The strongest and best-documented risk factor for drug hypersensitivity (DH) is the history of a previous reaction. Accidental exposures to drugs may lead to severe or even fatal reactions in sensitized patients. Preventable prescription errors are common. They are often due to inadequate medical history or poor risk assessment of recurrence of drug reaction. Proper documentation is essential information for the doctor to make sound therapeutic decision. The European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology have formed a task force and developed a drug allergy passport as well as general guidelines of drug allergy documentation. A drug allergy passport, a drug allergy alert card, a certificate, and a discharge letter after medical evaluation are adequate means to document DH in a patient. They are to be handed to the patient who is advised to carry the documentation at all times especially when away from home. A drug allergy passport should at least contain information on the culprit drug(s) including international nonproprietary name, clinical manifestations including severity, diagnostic measures, potential cross-reactivity, alternative drugs to prescribe, and where more detailed information can be obtained from the issuer. It should be given to patients only after full allergy workup. In the future, electronic prescription systems with alert functions will become more common and should include the same information as in paper-based documentation.
- MeSH
- čipové karty ve zdravotnictví * MeSH
- dokumentace * metody MeSH
- léková alergie diagnóza etiologie prevence a kontrola MeSH
- lidé MeSH
- průzkumy a dotazníky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa MeSH
Cíl: Stanovit koncentrace pro-atriálního natriuretického peptidu (pro-ANP) u pacientů v sepsi, těžké sepsi a septickém šoku. Zjistit diagnostickou a prognostickou významnost tohoto parametru u uvedených diagnóz. Zjistit korelace pro-ANP s dalšími parametry – interleukinem-6 (IL-6), interleukinem-8 (IL-8), interleukinem-10 (IL-10), prokalcitoninem (PCT), lipopolysacharid vázajícím proteinem (LBP), a fyziologickým skóre – APACHE II a SOFA. Typ studie: Observační, prospektivní. Název a sídla pracovišť: Oddělení klinické biochemie, hematologie a imunologie, Nemocnice Na Homolce, Praha, Anesteziologicko-resuscitační klinika, Thomayerova nemocnice, Praha, Anesteziologicko-resuscitační oddělení, Nemocnice Na Homolce, Praha. Materiál a metody: Do studie bylo zařazeno 28 nemocných přijatých na anesteziologicko-resuscitační oddělení splňujících kritéria sepse (n = 6), těžké sepse (n = 7) a septického šoku (n = 15). Imunoluminometrickou metodou byla u nich měřena do 24 hodin po splnění diagnostických kritérií koncentrace pro-atriálního natriuretického peptidu, společně s dalšími parametry – IL-6, IL-8, IL-10, PCT, LBP. Po prvním měření následovala v intervalu 2–4 dnů další měření po celou dobu hospitalizace na anesteziologicko-resuscitačním oddělení. Jako kontrolní skupina bylo vyšetřeno 12 vzorků zdravých lidí. Hodnotili jsme vztah pro-ANP k jednotlivým diagnózám, prognostickou významnost pro-ANP pro konečný klinický výsledek (přežití vs smrt). Koncentrace pro-ANP jsme korelovali s dvěma skórovacími systémy – APACHE II a SOFA. Výsledky: Nezjistili jsme statisticky významné rozdíly středních hodnot pro-ANP u jednotlivých diagnóz – sepse, těžké sepse a septického šoku (průměry: 636,7 pmol/l, 628,9 pmol/l, respektive 752,7 pmol/l; mediány: 378,8 pmol/l, 204 pmol/l, resp. 595 pmol/l). Koncentrace pro-ANP ve skupině přeživších v den přijetí se významně nelišila proti skupině zemřelých (medián 396,4 pmol/l, respektive 816,8 pmol/l, p = 0,077). Zjistili jsme statisticky významný rozdíl mezi první a poslední hodnotou pro-ANP ve skupině zemřelých (medián 816,8, respektive 1254,4 pmol/l, p = 0,01). Ve skupině přeživších tento rozdíl nebyl statisticky významný. Při hodnocení predikce konečného klinického výsledku (přežití vs smrt) ve vztahu ke koncentraci pro-ANP byla při hodnotě cutt off = 664 pmol/l (vstupní měření) senzitivita 41,7% a specificita 87,5%, plocha pod ROC křivkou byla 0,625. Při hodnotě cut-off = 503,4 pmol/l (poslední měření) byla senzitivita 83,3%, specificita 68,7%, plocha pod ROC křivkou byla 0,797. Zjistili jsme korelaci mezi hodnotami pro-ANP a klinickým skóre – APACHE II a SOFA ve skupině přeživších. Ve skupině zemřelých korelovala koncentrace pro-ANP pouze s APACHE II (r = 0,57, p < 0,0001). Korelaci jsme zjistili také ve skupině zemřelých mezi pro-ANP a prokalcitoninem. S dalšími měřenými parametry jsme korelaci pro-ANP neprokázali. Závěr: Neprokázali jsme statisticky významný rozdíl koncentrace pro-ANP ve vztahu k jednotlivým diagnózám – sepse, těžká sepse a septický šok. Koncentrace pro-ANP v den přijetí u přeživších se statisticky významně nelišila od skupiny zemřelých. Ve skupině zemřelých byla koncentrace pro-ANP v den přijetí statisticky významně nižší než poslední naměřená hodnota. Jsou nutné další studie k objasnění významnosti pro-ANP jako diagnostického a/nebo prognostického parametru u pacientů se sepsí, těžkou sepsí a septickým šokem.
Objective: To evaluate the concentration of pro-atrial natriuretic peptide in patients with sepsis, severe sepsis and septic shock. To assess the diagnostic and prognostic value of mid-regional pro-atrial natriuretic peptide (pro-ANP) levels with these diagnoses. To assess the correlation of pro-ANP levels with those of interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), procalcitonin (PCT), lipopolysaccharide-binding protein (LBP) and physiological scores – APACHE II and SOFA. Design: Observational, prospective. Setting: Department of Clinical Biochemistry, Hematology and Immunology, Hospital Na Homolce, Department of Anaesthesiology and Intensive Care, Thomayer’s Hospital, Prague, Department of Anaesthesiology and Intensive Care, Hospital Na Homolce, Prague. Material and Methods: Serum concentrations of pro-ANP were determined using the immunoluminometric assay in 28 patients admitted to the medical intensive care unit for sepsis (6), severe sepsis (7), and septic shock (15). Pro-ANP levels as well as those of PCT, IL-6, IL-8, IL-10 and LBP were measured on day 1 and during the course of their stay at the intensive care unit. The diagnostic and prognostic value of pro-ANP was compared with that of the Acute Physiology and Chronic Health Evaluation (APACHE II) and SOFA score. Mid-regional pro- ANP was detected in serum using immunoluminometric assay (ILMA). Pro-ANP was also determined in 12 healthy adults.Results: No significant differences of pro-ANP levels were found in patients with sepsis, severe sepsis and septic shock (385.3 pmol/l, 209 pmol/l and 888 pmol/l, respectively). On the day of admission, pro-ANP levels were not significantly different in survivors compared to non-survivors (median 396.4 pmol/l and 816.8 pmol/l, respectively, p = 0.077). In the group of non-survivors pro-ANP levels on the day of admission were significantly lower than pro-ANP levels taken on the last day of their stay on ICU median 816.8 and 1254.4 pmol/l, respectively, p = 0.0108). In a receiver operating characteristic curve analysis for survival, the cut-off 664 pmol/l on the day of admission had a sensitivity of 41.7% and specificity of 87.5%. The area under the curve (AUC) for pro-ANP was 0.625. The cut-of value of 503.4 pmol/l on the last day of their stay was found to have a sensitivity of 83.3% and specificity of 68.7%. The area under the curve was 0.797. We found the correlation between pro-ANP, SOFA and APACHE II score in survivors. In non-survivors only pro-ANP and APACHE II correlation was found. The correlation was determined between pro-ANP and procalcitonin in non- -survivors (r = 0.57, p < 0.0001). No correlation was found between pro-ANP and IL-6, IL-8, IL-10 and LBP. Conclusion: We did not find statistically significant differences of pro-ANP levels in patients with sepsis, severe sepsis and septic shock. Pro-ANP levels on the day of admission were not significantly different in survivors and non- -survivors. In the group of non-survivors pro-ANP levels on the day of admission were significantly lower than the last pro-ANP levels. Further studies are necessary for the evaluation of pro-ANP as a diagnostic and/or prognostic parameter in patients with sepsis, severe sepsis and septic shock.
