BACKGROUND AND AIM: Progress in laboratory diagnostics of IgE-mediated allergy is the use of component-resolved diagnosis. Our study analyses the results of specific IgE to 295 allergen reagents (117 allergenic extracts and 178 molecular components) in patients suffering from atopic dermatitis (AD) with the use of ALEX2 Allergy Explorer. METHOD: The complete dermatological and allergological examination, including the examination of the sensitization to molecular components with ALEX2 Allergy Explorer testing, was performed. The statistical analysis of results was performed with these methods: TURF (total unduplicated reach and frequency), best reach and frequency by group size, two-sided tests, Fisher's exact test, and chi-square test (at an expected minimum frequency of at least 5). RESULTS: Altogether, 100 atopic dermatitis patients were examined: 48 men, 52 women, the average age 40.9 years, min. age 14 years, max. age 67 years. The high and very high level of specific IgE was reached in 75.0% of patients to 18 molecular components: from PR-10 proteins (Aln g 1, Bet v 1, Cor a1.0103, Cor a1.0401, Fag s 1), lipocalin (Can f 1), NPC2 family (Der f 2, Der p 2), uteroglobin (Fel d 1), from Alternaria alternata (Alt a 1), Beta expansin (Lol p 1, Phl p 1), molecular components from Timothy, cultivated rye (Secc pollen) and peritrophin-like protein domain Der p 23. The high and very high level of specific IgE to other lipocalins (Fel d 7, Can f 4), to arginine kinase (Bla g 9, German cockroach), and to allergen extracts Art v (mugwort), and Cyn d (Bermuda grass) reached 52.0% of patients. The severity of AD is in significant relation to the sensitization to molecular components of storage mites (Gly d 2, Lep d 2-NPC2 family), lipocalins (Can f 1, Can f 2, Can f 4, and Can f 6), arginine kinase (Asp f 6, Bla g 9, Der p 20, Pen m 2), uteroglobin (Fel d 1, Ory c 3), Mn superoxide dismutase (Mala s 11), PR-10 proteins (Fag s 1, Mal d 1, Cor a 1.0401, Cor a 1.0103), molecular components of the peritrophin-like domain (Der p 21, Der p 23), and to Secc pollen. In the subgroup of patients suffering from bronchial asthma, the significant role play molecular components from house dust mites and storage mites (Lep d 2, Der p 2, Der f 2-NPC2 family), cysteine protease (Der p 1), peritrophin-like protein domain (Der p 21, Der p 23), enolase from Alternaria alternata (Alt a 6), and Beta expansin Phl p 1. CONCLUSION: The results of our study demonstrate the detailed profile of sensitization to allergens reagents (allergen extract and molecular components) in patients with atopic dermatitis. We show the significance of disturbed epidermal barrier, resulting in increased penetration of allergens. We confirmed the significant relationship between the severity of AD, the occurrence of bronchial asthma and allergic rhinitis, and high levels of specific IgE to allergen reagents. Our results may be important for regime measures and immunotherapy; Der p 23 shall be considered as an essential component for the diagnosis and specific immunotherapy of house dust mite allergy.

• MeSH
• alergeny MeSH
• alergická rýma diagnóza   imunologie   MeSH
• atopická dermatitida diagnóza   imunologie   MeSH
• bronchiální astma diagnóza   imunologie   MeSH
• dospělí MeSH
• imunoglobulin E analýza   metabolismus   MeSH
• kožní testy metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• pyl imunologie   MeSH
• Pyroglyphidae imunologie   MeSH
• senioři MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

Cílem sdělení je shrnutí současného přístupu k diagnostice Niemann-Pickovy choroby typu C (NP-C) s důrazem na nové laboratorní techniky. NP-C je závažné autozomálně recesivní neuroviscerální onemocnění a aktuální dostupnost terapie ovlivňující průběh nemoci zvyšuje důležitost její včasné diagnostiky. Dědičně podmíněný deficit transportního proteinu pro cholesterol (NPC1 nebo NPC2) u NP-C vede k poruše transportu lipidů uvnitř buňky. Ověření klinického podezření na NP-C se proto opírá o biochemické a/nebo molekulárně genetické metody. Nové metody využívajících analýzu biomarkerů v krevním séru nebo plazmě a pokročilé sekvenační techniky mají nyní v diagnostice NP-C důležitou roli. U části pacientů je pro ověření diagnózy nutné použít více vzájemně se doplňujících vyšetření, vč. v článku diskutovaných pokročilých buněčných a biochemických technik. Ty proto musí být k disposici ve specializované laboratoři.

This review provides a summary of current approaches to Niemann-Pick disease type C (NP-C) dianostics with an emphasis on novel laboratory techniques. NP-C is a severe autosomal recessive neurovisceral disorder and the recent availability of disease-modifying therapies increases the importance of its timely diagnosis. The hereditary deficiency of cholesterol transporter proteins (NPC1 or NPC2) in NP-C leads to abnormal intracellular lipid trafficking. Clinical suspicion for NP-C has to be confirmed by biochemical and/or molecular genetic methods. Novel biomarkers in serum or plasma and advanced sequencing techniques now have a prominent role in NP-C diagnostics. In a subset of patients, it is necessary to use several complementary techniques for confirmation of NP-C diagnosis, including advanced biochemical and cellular assays discussed in the paper. These methods therefore have to be available in a specialized laboratory.

• Klíčová slova
• filipinový test, lyzosfingolipidy, intracelulární transport cholesterolu,
• MeSH
• biologické markery MeSH
• lidé MeSH
• Niemannova-Pickova nemoc typu C * diagnóza   MeSH
• oxysteroly MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

Niemann-Pick type C (NPC) disease is a lysosomal storage disorder arising from mutations in the cholesterol-trafficking protein NPC1 (95%) or NPC2 (5%). These mutations result in accumulation of low-density lipoprotein-derived cholesterol in late endosomes/lysosomes, disruption of endocytic trafficking, and stalled autophagic flux. Additionally, NPC disease results in sphingolipid accumulation, yet it is unique among the sphingolipidoses because of the absence of mutations in the enzymes responsible for sphingolipid degradation. In this work, we examined the cause for sphingosine and sphingolipid accumulation in multiple cellular models of NPC disease and observed that the activity of sphingosine kinase 1 (SphK1), one of the two isoenzymes that phosphorylate sphingoid bases, was markedly reduced in both NPC1 mutant and NPC1 knockout cells. Conversely, SphK1 inhibition with the isotype-specific inhibitor SK1-I in WT cells induced accumulation of cholesterol and reduced cholesterol esterification. Of note, a novel SphK1 activator (SK1-A) that we have characterized decreased sphingoid base and complex sphingolipid accumulation and ameliorated autophagic defects in both NPC1 mutant and NPC1 knockout cells. Remarkably, in these cells, SK1-A also reduced cholesterol accumulation and increased cholesterol ester formation. Our results indicate that a SphK1 activator rescues aberrant cholesterol and sphingolipid storage and trafficking in NPC1 mutant cells. These observations highlight a previously unknown link between SphK1 activity, NPC1, and cholesterol trafficking and metabolism.

• MeSH
• buněčné linie MeSH
• cholesterol metabolismus   MeSH
• endozomy metabolismus   MeSH
• estery cholesterolu metabolismus   MeSH
• fibroblasty MeSH
• fosfotransferasy s alkoholovou skupinou jako akceptorem metabolismus   MeSH
• intracelulární signální peptidy a proteiny metabolismus   MeSH
• lidé MeSH
• lyzozomy metabolismus   MeSH
• membránové glykoproteiny metabolismus   MeSH
• myši MeSH
• Niemannova-Pickova nemoc typu C metabolismus   patofyziologie   MeSH
• primární buněčná kultura MeSH
• protein NPC1 genetika   metabolismus   MeSH
• sfingolipidy metabolismus   MeSH
• sfingosin genetika   metabolismus   MeSH
• transport proteinů MeSH
• transportní proteiny metabolismus   MeSH
• vezikulární transportní proteiny genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

BACKGROUND: Niemann-Pick type C (NP-C) is a rare neurovisceral genetic disorder caused by mutations in the NPC1 or the NPC2 gene. NPC1 is a multipass-transmembrane protein essential for egress of cholesterol from late endosomes/lysosomes. To evaluate impacts of NPC1 mutations, we examined fibroblast cultures from 26 NP-C1 patients with clinical phenotypes ranging from infantile to adult neurologic onset forms. The cells were tested with multiple assays including NPC1 mRNA expression levels and allele expression ratios, assessment of NPC1 promoter haplotypes, NPC1 protein levels, cellular cholesterol staining, localization of the mutant NPC1 proteins to lysosomes, and cholesterol/cholesteryl ester ratios. These results were correlated with phenotypes of the individual patients. RESULTS: Overall we identified 5 variant promoter haplotypes. Three of them showed reporter activity decreased down to 70% of the control sequence. None of the haplotypes were consistently associated with more severe clinical presentation of NP-C. Levels of transcripts carrying null NPC1 alleles were profoundly lower than levels of the missense variants. Low levels of the mutant NPC1 protein were identified in most samples. The protein localised to lysosomes in cultures expressing medium to normal NPC1 levels. Fibroblasts from patients with severe infantile phenotypes had higher cholesterol levels and higher cholesterol/cholesteryl ester ratios. On the contrary, cell lines from patients with juvenile and adolescent/adult phenotypes showed values comparable to controls. CONCLUSION: No single assay fully correlated with the disease severity. However, low residual levels of NPC1 protein and high cholesterol/cholesteryl ester ratios associated with severe disease. The results suggest not only low NPC1 expression due to non-sense mediated decay or low mutant protein stability, but also dysfunction of the stable mutant NPC1 as contributors to the intracellular lipid transport defect.

• MeSH
• fibroblasty metabolismus   MeSH
• intracelulární signální peptidy a proteiny MeSH
• lidé MeSH
• membránové glykoproteiny * genetika   metabolismus   MeSH
• mladiství MeSH
• mutace genetika   MeSH
• transportní proteiny * genetika   MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Niemann-Pick Type C (NPC) is a progressive and life limiting autosomal recessive disorder caused by mutations in either the NPC1 or NPC2 gene. Mutations in these genes are associated with abnormal endosomal-lysosomal trafficking, resulting in the accumulation of multiple tissue specific lipids in the lysosomes. The clinical spectrum of NPC disease ranges from a neonatal rapidly progressive fatal disorder to an adult-onset chronic neurodegenerative disease. The age of onset of the first (beyond 3 months of life) neurological symptom may predict the severity of the disease and determines life expectancy.NPC has an estimated incidence of ~ 1: 100,000 and the rarity of the disease translate into misdiagnosis, delayed diagnosis and barriers to good care. For these reasons, we have developed clinical guidelines that define standard of care for NPC patients, foster shared care arrangements between expert centres and family physicians, and empower patients. The information contained in these guidelines was obtained through a systematic review of the literature and the experiences of the authors in their care of patients with NPC. We adopted the Appraisal of Guidelines for Research & Evaluation (AGREE II) system as method of choice for the guideline development process. We made a series of conclusive statements and scored them according to level of evidence, strengths of recommendations and expert opinions. These guidelines can inform care providers, care funders, patients and their carers of best practice of care for patients with NPC. In addition, these guidelines have identified gaps in the knowledge that must be filled by future research. It is anticipated that the implementation of these guidelines will lead to a step change in the quality of care for patients with NPC irrespective of their geographical location.

• MeSH
• lidé MeSH
• Niemannova-Pickova nemoc typu C terapie   MeSH
• směrnice pro lékařskou praxi jako téma * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Background and Aims: The non-specific phospholipase C (NPC) is a new member of the plant phospholipase family that reacts to abiotic environmental stresses, such as phosphate deficiency, high salinity, heat and aluminium toxicity, and is involved in root development, silicon distribution and brassinolide signalling. Six NPC genes (NPC1-NPC6) are found in the Arabidopsis genome. The NPC2 isoform has not been experimentally characterized so far. Methods: The Arabidopsis NPC2 isoform was cloned and heterologously expressed in Escherichia coli. NPC2 enzyme activity was determined using fluorescent phosphatidylcholine as a substrate. Tissue expression and subcellular localization were analysed using GUS- and GFP-tagged NPC2. The expression patterns of NPC2 were analysed via quantitative real-time PCR. Independent homozygous transgenic plant lines overexpressing NPC2 under the control of a 35S promoter were generated, and reactive oxygen species were measured using a luminol-based assay. Key Results: The heterologously expressed protein possessed phospholipase C activity, being able to hydrolyse phosphatidylcholine to diacylglycerol. NPC2 tagged with GFP was predominantly localized to the Golgi apparatus in Arabidopsis roots. The level of NPC2 transcript is rapidly altered during plant immune responses and correlates with the activation of multiple layers of the plant defence system. Transcription of NPC2 decreased substantially after plant infiltration with Pseudomonas syringae, flagellin peptide flg22 and salicylic acid treatments and expression of the effector molecule AvrRpm1. The decrease in NPC2 transcript levels correlated with a decrease in NPC2 enzyme activity. NPC2-overexpressing mutants showed higher reactive oxygen species production triggered by flg22. Conclusions: This first experimental characterization of NPC2 provides new insights into the role of the non-specific phospholipase C protein family. The results suggest that NPC2 is involved in the response of Arabidopsis to P. syringae attack.

• MeSH
• Arabidopsis enzymologie   imunologie   mikrobiologie   MeSH
• fosfatidylcholiny metabolismus   MeSH
• fosfolipasy typu C fyziologie   MeSH
• Golgiho aparát enzymologie   MeSH
• imunita rostlin fyziologie   MeSH
• klonování DNA MeSH
• konfokální mikroskopie MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• nemoci rostlin imunologie   mikrobiologie   MeSH
• proteiny huseníčku fyziologie   MeSH
• protoplasty enzymologie   MeSH
• Pseudomonas syringae * MeSH
• reaktivní formy kyslíku MeSH
• regulace genové exprese u rostlin MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Major domestic mite allergens are present in feces. We present a detailed 2D-E-MS/MS proteomic analysis of the Dermatophagoides pteronyssinus feces. Precise cultivation yielded a pure fecal extract. We detected differences in fecal allergens/digestive enzymes between D. pteronyssinus and D. farinae using 2D-E fingerprinting, including unique information on species-specific protease isoforms. Proteomic analysis was performed by 2D-E coupled with MALDI-TOF/TOF identification. The species-specific differences in the fecal extracts of the mites were attributed to trypsin-like proteases known as group 3 allergens. In D. farinae, Der f 3 exhibited high abundance with a pI similar (acidic) to that of the cysteine protease Der f 1 and the chymotrypsin protease Der f 6, whereas in D. pteronyssinus, Der p 3 was rarely detected and exhibited low abundance only at basic pI. Moreover, Der p 9 was detected at a pI of ~ 10, in contrast to Der p 1 and Der p 6, suggesting different compartmentalization in the body. Overall, in D. pteronyssinus feces, allergens of groups 1, 2, 6, and 15 were quantitatively similar to those of D. farinae with the exception of the group 3 and 9 allergens. This work provides novel insights into mite-defecated proteins/digestive enzymes, which are important allergens. SIGNIFICANCE: Millions of people are affected by allergy and asthma, and their number is growing. In homes, the major triggers of allergy and asthma are the house dust mites Dermatophagoides farinae and D. pteronyssinus, and a clear understanding of the development of diseases caused by these mites is needed. The major sources of mite allergens are their feces, which are deposited in the environment and are easily inhaled as part of aeroplankton. However, descriptions of and comparisons between the major fecal allergens of these two mites are lacking. This study shows that similar group 1 (cysteine protease), 2 (NPC2 family), 6 (chymotrypsin) and 15 (chitinase-like) allergens are present in the feces of these two mite species, as determined by 2D-E mapping, whereas group 3 (trypsin) and 9 (collagenolytic protease) allergens in the feces of the two species are different. The results provide unique MS/MS mapped fingerprints of mite species-specific isoforms in feces. The presence of ubiquitin in mite feces suggests that these proteins participate in the post-translational modification of fecal proteins. The findings are essential for understanding differences between D. farinae and D. pteronyssinus with respect to immunoreactivity, protease activation mechanisms, association with microbes, and food utilization.

• MeSH
• 2D gelová elektroforéza MeSH
• alergeny analýza   MeSH
• Dermatophagoides farinae chemie   MeSH
• Dermatophagoides pteronyssinus chemie   MeSH
• druhová specificita MeSH
• feces chemie   MeSH
• protein - isoformy MeSH
• proteomika metody   MeSH
• tandemová hmotnostní spektrometrie MeSH
• trypsin MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

BACKGROUND: Niemann-Pick disease type C (NPC) is a rare, fatal neurovisceral disorder with autosomal recessive inheritance, and featuring striking clinical variability dependent on the age at onset of neurological symptoms. We report data from a large cohort of 56 Czech patients with NPC diagnosed over a period of 37 years. METHODS: An observational, retrospective analysis of historic and current clinical and laboratory information was performed among all NPC patients originating from the area of the contemporary Czech Republic and diagnosed between 1975 and 2012. All patients with ≥1 positive diagnostic test and relevant clinical information were included. Data on diagnostic methods (histopathological and/or ultrastructural; biochemical; genetic), clinical status and general information on treatment were collated. Data were examined in accordance with international guidelines for the management of NPC. RESULTS: Between 1975 and 1985 diagnoses were based exclusively on specific histopathological findings, often at autopsy. Bone marrow smear (BMS) analyses have proved to be a very specific indicator for NPC and have become an important part of our diagnostic algorithm. Filipin staining and cholesterol esterification assays became the definitive diagnostic tests after 1985 and were applied in 24 of our patients. Since 2005, more and more patients have been assessed using NPC1/NPC2 gene sequencing. Twelve patients were diagnosed with neonatal/early-infantile onset NPC, 13 with the late-infantile onset form, 20 with the juvenile onset form, and nine with the adolescent/adult onset form. Two diagnosed patients remained neurologically asymptomatic at study completion. Nineteen patients were siblings. Causal NPC1 mutations were determined in 38 patients; two identical NPC2 mutations were identified in one patient. In total, 30 different mutations were identified, 14 of which have been confirmed as novel. The frequency of individual mutated NPC1 alleles in our cohort differs compared with previous published data: the most frequent mutant NPC1 allele was p.R1186H (n = 13), followed by p.P1007A (n = 8), p.S954L (n = 8) and p.I1061T (n = 4). CONCLUSIONS: These data demonstrate the evolution of the diagnostic process in NPC over the last four decades. We estimate the contemporary birth prevalence of NPC in the Czech Republic at 0.93 per 100,000.

• MeSH
• lidé MeSH
• Niemannova-Pickova nemoc typu C diagnóza   epidemiologie   patofyziologie   MeSH
• retrospektivní studie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

Niemann-Pickova choroba typ C je autozomálně recesivně dědičné lysozomální onemocnění, klinicky charakterizované věkově specifickou symptomatologií, s možností manifestace od novorozeneckého věku do pozdní dospělosti. S výjimkou neonatální formy s cholestázou, respiračním selháním a hepatosplenomegalií jde v dalších věkových kategoriích o nemoc vysloveně neurodegenerativní, často doprovázenou splenomegalií. Příčinou je funkční porucha membránového systému pozdního endozomu/lysozomu s akumulací neesterifikovaného cholesterolu a glykosfingolipidů v důsledku mutací v genech NPC1 (95 % případů) nebo NPC2 (5 % případů), kódujících lysozomální membránový protein NPC1 a solubilní protein NPC2. Základem diagnostiky je správné zhodnocení klinických symptomů s přihlédnutím k věku nemocného. Podezření potvrdí specifické testy v tkáňové kultuře fibroblastů a/nebo molekulárně genetická analýza uvedených genů. Aktuální možnost léčby spočívá v podávání reverzibilního inhibitoru glukosylceramidsyntázy (miglustat), potenciálně stabilizujícího průběh nemoci, experimentálně slibná aplikace cyklodextrinu vstupuje do fáze klinického testování. Komplexní diagnostika je v ČR dostupná prostřednictvím Ústavu dědičných metabolických poruch (diagnóza stanovena u 67 pacientů, z toho 42 českých).

Niemann-Pick disease type C is an autosomal recessive lysosomal disorder clinically characterized by age-specific symptomatology with possible manifestation any time from neonatal age to late adulthood. Except for its neonatal form with cholestasis, respiratory failure and hepatosplenomegaly, the disease presents as a neurodegenerative disorder, frequently with splenomegaly. Pathophysiology involves dysfunction of the late endosome/lysosome membraneous system with accumulation of unesterified cholesterol and glycosphingolipids due to mutations in the NPC1 and NPC2 genes coding the corresponding lysosomal proteins. Results of clinical examination must be confirmed by specific loading tests in cultivated fibroblasts and/or molecular genetic analysis of the concerned genes. In the last years the disease is treated with a reversible glucosylceramide synthase inhibitor miglustat, potentially stabilizing its course. Recently, clinical testing of cyclodextrin has been initiated. In the Czech Republic, comprehensive diagnostics is available at The Institute of Inherited Metabolic Disorders (67 confirmed patients including 42 Czechs).

• Klíčová slova
• neesterifikovaný cholesterol, gen NPC1, gen NPC2, miglustat, cyklodextrin, ZAVESCA,
• MeSH
• 1-deoxynojirimycin analogy a deriváty   terapeutické užití   MeSH
• cholesterol metabolismus   MeSH
• cyklodextriny terapeutické užití   MeSH
• diagnostické techniky a postupy MeSH
• esterifikace MeSH
• financování organizované MeSH
• genetická predispozice k nemoci MeSH
• klinický obraz nemoci MeSH
• lidé MeSH
• membránové glykoproteiny genetika   MeSH
• Niemannova-Pickova nemoc typu C diagnóza   klasifikace   patofyziologie   MeSH
• prenatální diagnóza MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Niemannova-Pickova choroba typu C je autosomálně recesivně dědičné střídavé onemocnění vyskytující se panetnicky s incidencí cca 1 : 150 000. Genetická mutace genu NPC1 nebo NPC2 má za následek poruchu transportu a esterifikace cholesterolu uvnitř buňky. V lyzosomech se hromadí neesterifikovaný cholesterol, sfingomyelin, fosfolipidy a glykosfingolipidy Klinická manifestace Niemannovy-Pickovy choroby typu C je závislá na věku a projevy onemocnění zahrnují kromě hepatosplenomegalie mentální retardaci, poruchy chůze, kataplexii a ataxii doprovázené parézou vertikálního pohledu. Onemocnění nebývá pro variabilitu klinických projevů rozpoznáno, je nesprávně diagnostikováno nebo je zjištěno opožděně a postiženým bývá podávána nevhodná léčba. Plnému rozvoji onemocnění mohou předcházet psychotické příznaky, halucinace nebo agresivní chování. Vzhledem k tomu, že existuje léčba, je nezbytné zvýšit povědomí o této chorobě a její diagnostice tak, aby mohla být včas zahájena její adekvátní terapie.

Niemann-Pick disease type C is a rare and fatal inherited autosomal recessive disease caused by mutations in either the NPC1 or NPC2 genes and leads to the inhibition of unesterified cholesterol glycosphingolipids transport and intracellular accumulation in the brain, liver and spleen. Disease affects both infants and adults with neurological symptoms varying with age of onset. Symptoms include mental retardation, gait problems, cataplexy and ataxia with the most common characteristic being vertical supranuclear gaze palsy. People suffering from Niemann-Pick disease presenting with neuropsychiatric symptoms in combination with delayed onset are often misdiagnosed as other major psychiatric disorders and may thus be prescribed inappropriate treatments. Non-motor signs often precede the first notable clinical motor symptoms in adult Niemann-Pick disease including neuropsychiatric illness in the form of schizophrenia-like psychotic disorders, hallucinations or/and aggressive behaviours. Improved awareness of Niemann-Pick disease and its symptoms among clinicians is essential for better disease detection, since patients diagnosed with chronic psychiatric illness and concomitant neurological impairments managed with antipsychotic drugs may have this disease.

• Klíčová slova
• gen NPC2, gen NPC1, neuropsychiatrická onemocnění,
• MeSH
• 1-deoxynojirimycin analogy a deriváty   terapeutické užití   MeSH
• genetická predispozice k nemoci genetika   MeSH
• glykosfingolipidy MeSH
• lidé MeSH
• lyzozomální nemoci z ukládání diagnóza   terapie   MeSH
• membrány MeSH
• neurologické manifestace MeSH
• Niemannova-Pickova nemoc typu C diagnóza   genetika   metabolismus   MeSH
• pohyby očí genetika   MeSH
• psychotické poruchy epidemiologie   etiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH