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1.
Sci Rep ; 11(1): 20972, 2021 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-34697402

RESUMO

Acid sphingomyelinase deficiency (ASMD), historically known as Niemann-Pick disease (NPD) types A, A/B, and B, is a rare, progressive, potentially fatal lysosomal storage disease with a spectrum of phenotypes. Little is known about how ASMD symptoms affect the lives of patients and their caregivers. In a cross-sectional qualitative study conducted in the US and UK, and in collaboration with the National Niemann-Pick Disease Foundation (US) and Niemann-Pick UK, we investigated the symptom experience of patients with ASMD types B and A/B and explored how the disease impacts their and their caregivers' lives. The study included 17 adult patients (mean age 38.7 years, 12 female), three caregivers of adults with ASMD, 12 pediatric/adolescent patients with ASMD (mean age 10.5 years, six female), and 12 caregivers of pediatric/adolescent patients with ASMD. The most commonly reported disease manifestations were respiratory (n = 26, 89.7%), abdominal (n = 25, 86.2%), and musculoskeletal symptoms (n = 23, 79.3%); excessive bleeding or bruising (n = 20, 69%); fatigue (n = 20, 69%); gastrointestinal symptoms (n = 18, 62.1%); and headache (n = 15, 51.7%). ASMD was reported to negatively impact patients' physical function (n = 23, 79.3%), self-esteem (n = 18, 62.1%), emotions (n = 16, 55.2%), social function and relationships (n = 16, 55.2%), and personal care (n = 9, 31%). Providing care for individuals with ASMD negatively affected caregivers' emotional well-being (n = 12, 80%), social function (n = 4, 26.7%), relationships (n = 6, 40%), and financial security (n = 7, 46.7%). The physical toll of providing care, the need for lifestyle changes, and the responsibility for making medical decisions added to the burden for caregivers. Alternatively, some caregivers noted that caring for a loved one enhanced their spirituality, providing them with a different outlook on life and a deeper personal resolve. This study showed that ASMD is a substantial burden for patients and caregivers, with long-term physical, emotional, social, and financial impacts. The study confirmed commonly known manifestations of ASMD, especially respiratory problems, but also identified less recognized ones, such as dermatological complications. The data collected and insight gained from this study should enhance clinical care, help evaluate new treatments, and inform health care decision making for patients with ASMD.


Assuntos
Cuidadores/psicologia , Doenças de Niemann-Pick/psicologia , Qualidade de Vida/psicologia , Adolescente , Adulto , Criança , Pré-Escolar , Tomada de Decisão Clínica , Estudos Transversais , Feminino , Teoria Fundamentada , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa , Reino Unido , Estados Unidos , Adulto Jovem
2.
Cogn Neuropsychol ; 35(3-4): 209-222, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28662611

RESUMO

Niemann-Pick disease type C (NPC) is a rare lysosomal storage disorder causing an intracellular lipid trafficking defect and varying damage to the spleen, liver, and central nervous system. The adult form, representing approximately 20% of the cases, is associated with progressive cognitive decline. Intriguingly, brains of adult NPC patients exhibit neurofibrillary tangles, a characteristic hallmark of Alzheimer's disease (AD). However, the cognitive, psychiatric, and neuropathological features of adult NPC and their relation to AD have yet to be explored. We systematically reviewed the literature on adult NPC with a particular focus on cognitive and neuroanatomical abnormalities. The careful study of cognition in adult NPC allows drawing critical insights in our understanding of the pathophysiology of AD as well as normal cognition.


Assuntos
Doença de Alzheimer/diagnóstico , Encéfalo/patologia , Doenças de Niemann-Pick/complicações , Adulto , Doença de Alzheimer/patologia , Feminino , Humanos , Masculino , Doenças de Niemann-Pick/patologia , Doenças de Niemann-Pick/psicologia
3.
Neuropsychopharmacol Hung ; 15(2): 95-103, 2013 Jun.
Artigo em Húngaro | MEDLINE | ID: mdl-23817360

RESUMO

Niemann-Pick disease (NPD) is a group of distinct rare disorders (i.e. NPD-A; NPD-B; NPD-C) - with autosomal recessive inheritance pattern - within the class of the inborn disorders of the sphingolipid metabolism (called sphingolipidoses). Since patients with NPD-A do not survive into adulthood and most patients with NPD-B are free from neuropsychiatric symptoms we discuss only briefly type-A and -B NPD and mainly constrict our review discussing the neuropsychiatric symptoms along with the pathomechanism and the treatment of NPD-C. NPD-C is clinically heterogeneous, with notable variations in age at onset, course and symptoms. Along with systemic signs, neurologic and psychiatric symptoms are quite frequent in NPD-C and in its adult form sometimes psychiatric symptoms are the first ones appearing. Unfortunately, the majority of clinicans (including adult psychiatrists and neurologists) are not aware of the symptom group characteristic to NPD-C so patients with this disorder are frequently misdiagnosed in the clinical practice. Since neuropsychiatric manifestations of NPD-C may be treated with a substrate reduction agent (miglustat) with greater awareness of the identification of neuropsychiatric symptoms in due course is the prerequisite of proper and early diagnosis and treatment.


Assuntos
Doenças de Niemann-Pick/diagnóstico , Doenças de Niemann-Pick/psicologia , 1-Desoxinojirimicina/análogos & derivados , 1-Desoxinojirimicina/uso terapêutico , Idade de Início , Cataplexia/etiologia , Transtornos Cognitivos/etiologia , Inibidores Enzimáticos/uso terapêutico , Humanos , Doença de Niemann-Pick Tipo A/diagnóstico , Doença de Niemann-Pick Tipo A/psicologia , Doença de Niemann-Pick Tipo B/diagnóstico , Doença de Niemann-Pick Tipo B/psicologia , Doença de Niemann-Pick Tipo C/diagnóstico , Doença de Niemann-Pick Tipo C/psicologia , Doenças de Niemann-Pick/tratamento farmacológico , Doenças de Niemann-Pick/enzimologia , Doenças de Niemann-Pick/genética , Esfingolipídeos/metabolismo , Esfingomielina Fosfodiesterase/deficiência , Esfingomielina Fosfodiesterase/metabolismo
4.
J Inherit Metab Dis ; 30(1): 60-7, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17160616

RESUMO

Niemann-Pick type C disease is a fatal neurovisceral disorder linked to dysregulation in cholesterol processing. A medication for this disease is currently being tested in clinical trials. However, there is a lack of information on neuropsychological testing parameters for this disease. One aim of this pilot study was to evaluate a test battery that could be used to assess cognitive deficits in different stages of the disease. A second aim was to determine whether specific functional deficits are associated with certain disease stages. Eight men and two women (19-40 years of age) harbouring mutations in the gene coding for the cholesterol trafficking protein NPC1 were put through the same test battery independently of their disease stage. The external staging criterion was based on a five-step clinical scale. Trail Making tests A & B and verbal fluency were sensitive indicators at early stages of NPC. Corsi Block-Tapping, Mini Mental Status, Find Similarities and Clock Drawing showed abnormal results in patients with advanced disease. The Grooved Pegboard, Trail Making and Mosaic tests were unsuitable in advanced disease due to impaired fine motor skills. We observed that visuospatial working memory was less affected by the neurodegenerative process than verbal working memory. The series of tests used here could be supplemented by the severe impairment battery and Raven matrices tests for patients with advanced disease.


Assuntos
Proteínas de Transporte/genética , Glicoproteínas de Membrana/genética , Mutação , Doenças de Niemann-Pick/diagnóstico , Doenças de Niemann-Pick/genética , Doenças de Niemann-Pick/psicologia , Adulto , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Memória , Destreza Motora , Testes Neuropsicológicos , Proteína C1 de Niemann-Pick , Fatores de Tempo
5.
Neurology ; 66(2): 228-32, 2006 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-16434659

RESUMO

OBJECTIVE: To describe the disease course and natural history of Type A Niemann-Pick disease (NPD). METHODS: Ten patients with NPD-A (six male, four female; age range at entry: 3 to 6 months) were serially evaluated including clinical neurologic, ophthalmologic, and physical examinations, and assessment of development. Laboratory analyses, abdominal and brain ultrasounds, and chest radiographs also were obtained and information on intercurrent illnesses and cause of mortality was collected. RESULTS: All affected infants had a normal neonatal course and early development. The first symptom detected in all patients was hepatosplenomegaly. Developmental age did not progress beyond 10 months for adaptive behavior, 12 months for expressive language, 9 months for gross motor skills, and 10 months for fine motor skills. Non-neurologic symptoms included frequent vomiting, failure to thrive, respiratory infections, irritability, and sleep disturbance. Neurologic examination at the time of presentation was normal in most patients. Later neurologic examinations revealed progressive hypotonia with loss of the deep tendon reflexes. All patients had cherry red spots by 12 months. The median time from diagnosis to death was 21 months. The cause of death was respiratory failure in nine patients and complications from bleeding in the tenth. CONCLUSIONS: The clinical course in Type A Niemann-Pick disease is similar among affected patients and is characterized by a relentless neurodegenerative course that leads to death, usually within 3 years.


Assuntos
Hipotonia Muscular/etiologia , Doenças Neurodegenerativas/complicações , Doenças Neurodegenerativas/fisiopatologia , Doenças de Niemann-Pick/complicações , Doenças de Niemann-Pick/fisiopatologia , Insuficiência Respiratória/etiologia , Desenvolvimento Infantil , Feminino , Humanos , Lactente , Comportamento do Lactente , Desenvolvimento da Linguagem , Longevidade , Masculino , Destreza Motora , Hipotonia Muscular/fisiopatologia , Doenças Neurodegenerativas/psicologia , Doenças de Niemann-Pick/classificação , Doenças de Niemann-Pick/psicologia , Reflexo de Estiramento , Insuficiência Respiratória/mortalidade
7.
Rev Neurol (Paris) ; 161(3): 318-22, 2005 Mar.
Artigo em Francês | MEDLINE | ID: mdl-15800453

RESUMO

INTRODUCTION: Niemann-Pick Type C disease (NPC) is an autosomal recessive neurovisceral lysosomal lipid storage disorder. CASE REPORT: A 31-year-old right-handed woman had suffered from schizophrenia for 13 years. At 25 years of age, she developed a gait disorder with a static and kinetic cerebellar syndrome, dysarthria, vertical supranuclear gaze palsy and cognitive impairment. Brain MRI was normal. Abdominal ultrasonography was performed because of hypercholesterolemia and elevated transaminases and revealed hepatosplenomegaly, which in conjunction with other signs and symptoms, suggested the diagnosis of NPC. The diagnosis was confirmed by demonstration of lysosomal storage of unesterified cholesterol (filipin staining) and of a reduced rate of LDL-induced cholesterol esterification. Implication of the NPC1 gene was assessed by genetic complementation analysis. DISCUSSION: The phenotypic presentation of NPC is remarkably variable. The rarer adult-onset form has a slowly progressive course. Psychotic manifestations are often prominent and may precede neurologic symptoms. Exposure to neuroleptics delays the diagnosis of NPC. CONCLUSION: Psychotic manifestations associated with cerebellar syndrome, vertical supranuclear gaze palsy, and splenomegaly are very suggestive of NPC disease which can be reliably diagnosed on cultured skin fibroblasts by filipin staining.


Assuntos
Transtornos Mentais/psicologia , Doenças de Niemann-Pick/psicologia , Adulto , Antibacterianos , Feminino , Fibroblastos/patologia , Filipina , Humanos , Testes de Função Hepática , Imageamento por Ressonância Magnética , Transtornos Mentais/etiologia , Doenças de Niemann-Pick/complicações , Doenças de Niemann-Pick/diagnóstico , Esquizofrenia/complicações
9.
J Inherit Metab Dis ; 25(6): 491-500, 2002 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12555942

RESUMO

Although it is often perceived as a paediatric disorder, significant numbers of patients with Niemann-Pick disease type C present for the first time in adult life or survive into adult life. The presentation in these patients differs from that seen in the classical juvenile form of the disease. Adult patients are often referred to clinicians with psychosis or other major psychiatric problems. The dystonia with preserved intellectual functioning can be mistaken for other basal ganglia disorders such as Wilson disease. The presence of vertical gaze palsy is an important clinical clue and, in the presence of a modest increase in plasma chitotriosidase activity, can be very helpful in the differential diagnosis. The diagnosis should be confirmed in suspected cases by filipin staining of cultured fibroblasts, as well as cholesterol esterification studies and DNA mutation analysis.


Assuntos
Doenças de Niemann-Pick/fisiopatologia , Adolescente , Adulto , Ataxia/etiologia , Criança , DNA/genética , Progressão da Doença , Evolução Fatal , Feminino , Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/fisiopatologia , Hepatite/patologia , Humanos , Recém-Nascido , Testes de Inteligência , Masculino , Doenças de Niemann-Pick/genética , Doenças de Niemann-Pick/psicologia , Gravidez , Transtornos Psicóticos/etiologia , Convulsões , Esplenomegalia/etiologia , Tremor/fisiopatologia
10.
Dev Med Child Neurol ; 40(2): 126-9, 1998 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9489503

RESUMO

This study reports the case of a 16-year-old male who presented with a history of prominent psychotic symptoms and paranoid delusions which overshadowed subtle signs and symptoms of cognitive and motor dysfunction. Intensive neurobehavioral and biochemical investigations eventually led to the diagnosis of Niemann-Pick disease, type C (NPC), an autosomal recessively inherited storage disease that is associated with the accumulation of cholesterol in lysosomes and difficulties in the processing of exogenously derived cholesterol. Clues to the presence of a neurological disorder included: a history of insidiously declining academic and athletic performance which antedated the onset of psychosis; abnormalities on mental status examination, including psychomotor slowing, memory difficulties, and impairment of higher attentional functions; physical findings of subtle downgaze impairment, mild symmetrical hyperreflexia, and lower-extremity hypertonia with flexor plantar responses, marked impairment of upper-extremity rapid alternating movements, action tremor, and bilateral posturing with stress gait maneuvers. This case demonstrates the importance of careful and persistent neurodiagnostic evaluation in adolescents with psychotic presentations, particularly when cognitive and motor deterioration is suspected, and even when head CT and MRI scans are judged to be normal.


Assuntos
Delusões/diagnóstico , Delusões/etiologia , Doenças de Niemann-Pick/diagnóstico , Doenças de Niemann-Pick/psicologia , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/etiologia , Adolescente , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Diagnóstico Diferencial , Humanos , Masculino , Testes Neuropsicológicos , Transtornos Psicomotores/diagnóstico , Transtornos Psicomotores/etiologia
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