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1.
BMC Nephrol ; 25(1): 188, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831308

RESUMO

BACKGROUND: Long-term enzyme replacement therapy (ERT) may improve prognosis in the patients with Fabry disease (FD), however, detail psychosocial burden has not been focused on long life expectancy. We experienced a male case of FD under ERT, he was placed on hemodialysis and presented rapidly progressive cognitive function. CASE PRESENTATION: A 51-year-old male patient with FD has been receiving ERT from age of 38 years. Hemodialysis was initiated at the age of 47 years. The patient experienced several attacks of cerebral infarction, and brain images demonstrated wide-spread asymptomatic ischemic lesions. His behavior became problematic at the age of 51 years. He often exhibited restlessness during hemodialysis sessions and failure to communicate effectively. The patient experienced impairment of attention and executive function, topographical disorientation, and amnesia. Consequently, it was necessary for medical staff and family members to monitor his behavior for safe extracorporeal circulation and daily life activities. Annual standardized neuropsychiatric testing revealed worsening of cognitive performance. CONCLUSIONS: Despite treating with long-term ERT, it is necessary to determine the psychosocial burden derived from the progression of cognitive impairment in patients with FD undergoing hemodialysis.


Assuntos
Disfunção Cognitiva , Terapia de Reposição de Enzimas , Doença de Fabry , Diálise Renal , Humanos , Masculino , Doença de Fabry/psicologia , Doença de Fabry/complicações , Diálise Renal/psicologia , Pessoa de Meia-Idade , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/psicologia , Progressão da Doença , Efeitos Psicossociais da Doença
2.
J Inherit Metab Dis ; 45(4): 782-795, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34994980

RESUMO

Fabry disease (FD) is an X-linked lysosomal storage disorder with multi-system involvement including cerebrovascular disease. Patients with FD also have a high risk of ischaemic stroke and TIA. White matter hyperintensities are common, but their clinical impact on cognition remains uncertain. Previous studies have examined the neuropsychological profile of FD, but have been inconclusive in part due to methodological limitations including small sample sizes. We sought to address these limitations in a case-control study of 26 patients with Fabry disease with mild to moderate disease symptoms matched with 18 healthy controls for age and premorbid intellectual level. We obtained detailed neuropsychological data and MRI neuroimaging data on the severity of white matter changes. Mood was accounted for as a possible confounder. Our results showed significant compromise of executive functions and information processing speed for the FD group. Error analyses suggested that the compromise of executive functions could not be entirely accounted for by slowed information processing speed. We demonstrated significant correlations between cognitive decline and the overall volume of white matter hyperintensities in the FD group. Our results point to significant compromise of cognition in FD even without stroke or mood difficulties. This suggests that neuropsychological assessment and rehabilitation should be routinely offered to patients with FD.


Assuntos
Isquemia Encefálica , Disfunção Cognitiva , Doença de Fabry , Acidente Vascular Cerebral , Substância Branca , Estudos de Casos e Controles , Disfunção Cognitiva/etiologia , Doença de Fabry/complicações , Doença de Fabry/psicologia , Humanos , Imageamento por Ressonância Magnética , Testes Neuropsicológicos , Acidente Vascular Cerebral/etiologia , Substância Branca/diagnóstico por imagem
3.
Brain Res Bull ; 175: 158-167, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34339779

RESUMO

Fabry disease (FD) is an X-linked inherited disorder characterized by glycosphingolipid accumulation due to deficiency of α-galactosidase A (α-Gal A) enzyme. Chronic pain and mood disorders frequently coexist in FD clinical setting, however underlying pathophysiologic mechanisms are still unclear. Here we investigated the mechanical and thermal sensitivity in α-Gal A (-/0) hemizygous male and the α-Gal A (-/-) homozygous female mice. We also characterized the gene expression of dynorphinergic, nociceptinergic and CRFergic systems, known to be involved in pain control and mood disorders, in the prefrontal cortex, amygdala and thalamus of α-Gal A (-/0) hemizygous male and the α-Gal A (-/-) homozygous female mice. Moreover, KOP receptor protein levels were evaluated in the same areas. Fabry knock-out male, but not female, mice displayed a decreased pain threshold in both mechanical and thermal tests compared to their wild type littermates. In the amygdala and prefrontal cortex, we observed a decrease of pDYN mRNA levels in males, whereas an increase was assessed in females, thus suggesting sex-related dysregulation of stress coping and pain mechanisms. Elevated mRNA levels for pDYN/KOP and CRF/CRFR1 systems were observed in male and female thalamus, a critical crossroad for both painful signals and cognitive/emotional processes. KOP receptor protein level changes assessed in the investigated areas, appeared mostly in agreement with KOP gene expression alterations. Our data suggest that α-Gal A enzyme deficiency in male and female mice is associated with distinct neuropeptide gene and protein expression dysregulations of investigated systems, possibly related to the neuroplasticity underlying the neurological features of FD.


Assuntos
Comportamento Animal , Doença de Fabry/psicologia , Neuropeptídeos/metabolismo , Nociceptividade , Animais , Química Encefálica/genética , Hormônio Liberador da Corticotropina , Dinorfinas/genética , Feminino , Expressão Gênica , Masculino , Camundongos , Camundongos Knockout , Nociceptores , Limiar da Dor , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Receptores Opioides kappa/genética , Caracteres Sexuais
4.
Acta Neurol Belg ; 121(1): 191-197, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32915382

RESUMO

Fabry disease (FD) is a X-linked multi-systemic metabolic disorder with mainly renal, cardiac and neurological dysfunction. The neuropsychological impact is still unclear, with previous study results ranging from disturbance of speed of information processing and executive functions to a normal cognitive profile. The aim of our study was to gain further insight into the neuropsychological involvement of FD. Patients with genetically proven FD were enrolled at the Ghent University Hospital by their treating neurologist. We evaluated the cognitive status of each patient by a thorough neuropsychological test battery and these exact same neuropsychological assessments were repeated after a follow-up period of 2-4 years and at a second follow-up moment 1-4 years after the first follow-up. Thirteen patients with FD were included (8 female) with mean age of 41.5 years (SD ± 13.9) at baseline. All patients had normal neuropsychological test results on the subtests included in the cognitive battery at baseline, according to age-, gender- and education matched normative data. At the first follow-up moment (2-4 years after baseline), six patients were included (3 male), mean age 45.3 years. At the second follow-up (1-4 years after first follow-up), four patients (2 male) were included, with mean age 45 years. Both at the first and second follow-up moments, all patients obtained normal scores on the subtests. The cognitive functioning appeared to be in the normal range at baseline and did not decline over a follow-up period of 3-8 years, suggesting that cognition in FD patients may be well-preserved in time.


Assuntos
Cognição/fisiologia , Doença de Fabry/diagnóstico , Doença de Fabry/psicologia , Testes Neuropsicológicos , Adulto , Idoso , Função Executiva/fisiologia , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
5.
Brain ; 143(11): 3331-3342, 2020 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-33141169

RESUMO

Cerebral white matter pathology is a common CNS manifestation of Fabry disease, visualized as white matter hyperintensities on MRI in 42-81% of patients. Diffusion tensor imaging (DTI) MRI is a sensitive technique to quantify microstructural damage within the white matter with potential value as a disease biomarker. We evaluated the pattern of DTI abnormalities in Fabry disease, and their correlations with cognitive impairment, mood, anxiety, disease severity and plasma lyso-Gb3 levels in 31 patients with genetically proven Fabry disease and 19 age-matched healthy control subjects. We obtained average values of fractional anisotropy and mean diffusivity within the white matter and performed voxelwise analysis with tract-based spatial statistics. Using a standardized neuropsychological test battery, we assessed processing speed, executive function, anxiety, depression and disease severity. The mean age (% male) was 44.1 (45%) for patients with Fabry disease and 37.4 (53%) for the healthy control group. In patients with Fabry disease, compared to healthy controls the mean average white matter fractional anisotropy was lower in [0.423 (standard deviation, SD 0.023) versus 0.446 (SD 0.016), P = 0.002] while mean average white matter mean diffusivity was higher (749 × 10-6 mm2/s (SD 32 × 10-6) versus 720 × 10-6 mm2/s (SD 21 × 10-6), P = 0.004]. Voxelwise statistics showed that the diffusion abnormalities for both fractional anisotropy and mean diffusivity were anatomically widespread. A lesion probability map showed that white matter hyperintensities also had a wide anatomical distribution with a predilection for the posterior centrum semiovale. However, diffusion abnormalities in Fabry disease were not restricted to lesional tissue; compared to healthy controls, the normal appearing white matter in patients with Fabry disease had reduced fractional anisotropy [0.422 (SD 0.022) versus 0.443 (SD 0.017) P = 0.003] and increased mean diffusivity [747 × 10-6 mm2/s (SD 26 × 10-6) versus 723 × 10-6 mm2/s (SD 22 × 10-6), P = 0.008]. Within patients, average white matter fractional anisotropy and white matter lesion volume showed statistically significant correlations with Digit Symbol Coding Test score (r = 0.558, P = 0.001; and r = -0.633, P ≤ 0.001, respectively). Average white matter fractional anisotropy correlated with the overall Mainz Severity Score Index (r = -0.661, P ≤ 0.001), while average white matter mean diffusivity showed a strong correlation with plasma lyso-Gb3 levels (r = 0.559, P = 0.001). Our findings using DTI confirm widespread areas of microstructural white matter disruption in Fabry disease, extending beyond white matter hyperintensities seen on conventional MRI. Moreover, diffusion measures show strong correlations with cognition (processing speed), clinical disease severity and a putative plasma biomarker of disease activity, making them promising quantitative biomarkers for monitoring Fabry disease severity and progression.


Assuntos
Doença de Fabry/diagnóstico por imagem , Doença de Fabry/psicologia , Substância Branca/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Ansiedade/etiologia , Ansiedade/psicologia , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/psicologia , Depressão/etiologia , Depressão/psicologia , Imagem de Tensor de Difusão , Função Executiva , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/etiologia , Transtornos do Humor/psicologia , Testes Neuropsicológicos , Triexosilceramidas/sangue , Adulto Jovem
6.
J Inherit Metab Dis ; 43(5): 1070-1081, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32510623

RESUMO

Patients with Fabry disease (FD) have a high prevalence of depressive symptoms and can suffer from cognitive impairment, negatively affecting their life. The course of cognitive functioning and depressive symptoms in FD is unknown. The aim of this prospective cohort study was to describe changes in cognitive functioning and depressive symptoms and to identify related variables in patients with FD over 1 year. Assessments were conducted twice, using a neuropsychological test battery and the Centre of Epidemiological Studies Depression scale (CESD). Eighty-one patients were included of which 76 patients (94%) completed both assessments (age: 44 years, 34% men, 75% classical phenotype). A significant decrease in cognitive functioning was found in four patients (5%), with patients regressing from excellent to average/good. Changes were not related to sex, phenotype, stroke, IQ or CESD scores. CESD scores ≥16 were present in 29 patients (38%) at baseline. Using the reliable change index a decrease in CESD scores was found in six patients (8%). Decreased CESD scores were independently related to employing a positive and problem solving coping style and increased CESD scores to an avoiding and brooding coping style and worsening health perception. We found no major changes in cognitive functioning in patients with FD during 1 year follow-up making it an unsuitable outcome in FD treatment trials. Considering the high prevalence of persistent depressive symptoms, assessment of depressive symptoms should be part of routine follow-up. Altering coping styles and health perception may improve psychological well-being in FD.


Assuntos
Disfunção Cognitiva/diagnóstico , Depressão/diagnóstico , Transtorno Depressivo/diagnóstico , Doença de Fabry/fisiopatologia , Doença de Fabry/psicologia , Adaptação Psicológica , Adulto , Idoso , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Depressão/etiologia , Transtorno Depressivo/etiologia , Doença de Fabry/complicações , Feminino , Seguimentos , Humanos , Modelos Lineares , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Dor/etiologia , Estudos Prospectivos , Qualidade de Vida , Acidente Vascular Cerebral/complicações , Adulto Jovem
7.
Orphanet J Rare Dis ; 15(1): 28, 2020 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-31992347

RESUMO

BACKGROUND: Despite the high prevalence of depressive symptoms in Fabry disease (FD), it is unclear which patient characteristics are important in relation to these symptoms. Additionally, the impact of coping styles in relation to depressive symptoms in FD has been unexplored. Determining the impact of different factors relating to depressive symptoms in FD can guide both prevention and treatment of these symptoms. METHODS: Depressive symptoms (Center for Epidemiologic Studies Depression scale (CESD)) and coping styles (Utrecht Coping List) were assessed in a Dutch FD cohort. Other potentially important variables were identified from FD literature and assessed in this cohort. Relations were evaluated using multiple linear models. RESULTS: Potentially important variables in FD literature were: pain, unemployment, health perception, being single, comorbidities and stroke. Employed coping styles were "avoidance and brooding", "positivity and problem solving" and "seeking social support". Thirty-one of the 81 FD patients (38%) had depressive symptoms. CESD-scores were lower in patients with better health perception and more "positivity and problem solving" and higher in patients with more pain and "avoidance and brooding". The best model explained 70% (95%CI: 54-76%) of observed variance of the CESD. CONCLUSIONS: Depressive symptoms in FD are related to pain, negative health perception and use of specific coping styles. Psychological interventions could be employed to alter coping behavior and alleviate depressive symptoms.


Assuntos
Depressão/fisiopatologia , Depressão/psicologia , Doença de Fabry/fisiopatologia , Doença de Fabry/psicologia , Dor/fisiopatologia , Dor/psicologia , Adulto , Idoso , Encéfalo/fisiopatologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
8.
Sleep Breath ; 24(1): 95-101, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30937718

RESUMO

STUDY OBJECTIVES: Patients with Fabry disease (FD) report impaired quality of life and excessive daytime sleepiness. Obstructive sleep apnea (OSA) is frequently reported among patients with FD; however, its prevalence and its influence on quality of life and daytime sleepiness in this population are unclear. METHODS: Patients with FD in a cohort from the University Hospital Zurich (n = 52) were one-to-two matched to healthy adult controls (n = 104) according to age, sex, and body mass index. Participants underwent structured interviews (including Short Form-36) and level-3 respiratory polygraphy. An apnea-hypopnea index of ≥ 5/h was defined as OSA and the severity of FD was quantified with the Mainz Severity Score Index (MSSI). Conditional logistic regression was used to compare the outcomes. RESULTS: In patients with FD the mean MSSI was 13.3 ± 10.5 points and OSA prevalence was 19.2% vs. 9.0% in the matched control group (p = 0.09). The apnea-hypopnea index was significantly higher in patients with FD than in the control group (0.5/h [0.2-3.0] vs. 0.2/h [0.1-1.8], p = 0.026). OSA severity was associated with impaired quality of life in four dimensions for the whole study population. Furthermore, patients with FD did report significantly higher daytime sleepiness (Epworth Sleepiness Scale 7.6 points vs. 6.3 points; p = 0.01) than healthy controls. CONCLUSION: Patients with mild FD do not have a higher OSA prevalence than matched control subjects. Differences in OSA severity did not reach clinical significance. Further studies are warranted to determine the impact of OSA in patients with moderate-to-severe FD.


Assuntos
Doença de Fabry/diagnóstico , Doença de Fabry/psicologia , Qualidade de Vida/psicologia , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/psicologia , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Valores de Referência
9.
Adv Ther ; 36(10): 2866-2880, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31435831

RESUMO

INTRODUCTION: Fabry disease is an X-linked lysosomal storage disorder caused by a deficiency of α-galactosidase A. Symptoms include neuropathic pain and gastrointestinal problems, such as diarrhoea. To inform and support the design of a Phase III clinical trial for a new oral treatment for Fabry disease, this study evaluated patients' experiences of Fabry disease symptoms, the impact of symptoms on their quality of life, and their views on participating in clinical trials. METHODS: An online survey questionnaire was distributed to patients with Fabry disease, through relevant patient organisations. The questionnaire consisted mainly of quantitative, closed questions with pre-defined response options. Fabry-specific pain intensity and its impact on quality of life were rated on a scale from 0 to 10. RESULTS: In total, 367 patients completed the survey, of whom half reported frequent pain, moderate to severe pain, and pain in their hands and feet. Pain frequency, intensity and location were similar for males and females. There was no clear association between Fabry-specific pain and the use of enzyme replacement therapy (ERT), with moderate to severe pain reported by 80.4% of participants receiving ERT and by 75.0% of participants not receiving ERT. Of participants who were receiving ERT, 35.7% said they were willing to discontinue it to take part in a clinical trial testing a new oral drug for treating Fabry disease. Gastrointestinal symptoms were more heterogeneous in nature and frequency than Fabry-specific pain, but still affected a significant proportion of participants. CONCLUSIONS: Both male and female patients with Fabry disease experience significant Fabry-specific pain, which affects their quality of life. Furthermore, frequent diarrhoea affects many patients. The symptoms occur independently of the use of ERT. This suggests the healthcare needs of patients with Fabry disease are not being fully met, and additional treatments are required to improve symptoms and quality of life. FUNDING: This study was sponsored by Actelion Pharmaceuticals Ltd. Study sponsorship was transferred to Idorsia Pharmaceuticals Ltd in July 2018.


Assuntos
Terapia de Reposição de Enzimas/métodos , Doença de Fabry/tratamento farmacológico , Doença de Fabry/psicologia , Gastroenteropatias/tratamento farmacológico , Gastroenteropatias/psicologia , Qualidade de Vida/psicologia , alfa-Galactosidase/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Ensaios Clínicos como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
10.
Hum Brain Mapp ; 39(4): 1755-1764, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29315984

RESUMO

Aim of the study was to evaluate the presence of Default Mode Network (DMN) modifications in Fabry Disease (FD), and their possible correlations with structural alterations and neuropsychological scores. Thirty-two FD patients with a genetically confirmed diagnosis of classical FD (12 males, mean age 43.3 ± 12.2) were enrolled, along with 35 healthy controls (HC) of comparable age and sex (14 males, mean age 42.1 ± 14.5). Resting-State fMRI data were analyzed using a seed-based approach, with six different seeds sampling the main hubs of the DMN. Structural modifications were assessed by means of Voxel-Based Morphometry (VBM) and Tract-Based Spatial Statistics analyses. Between-group differences and correlations with neuropsychological variables were probed voxelwise over the whole brain. Possible correlations between FC modifications and global measures of microstructural alteration were also tested in FD patients with a partial correlation analysis. In the FD group, clusters of increased functional connectivity involving both supratentorial and infratentorial regions emerged, partially correlated to the widespread white matter (WM) damage found in these patients. No gray matter volume differences were found at VBM between the two groups. The connectivity between right inferior frontal gyrus and precuneus was significantly correlated with the Corsi block-tapping test results (p = .0001). Widespread DMN changes are present in FD patients that correlate with WM alterations and cognitive performance. Our results confirm the current view of a cerebral involvement in FD patients not simply associated to major cerebrovascular events, but also related to significant and diffuse microstructural and functional changes.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Doença de Fabry/diagnóstico por imagem , Doença de Fabry/fisiopatologia , Imageamento por Ressonância Magnética , Adulto , Idoso , Mapeamento Encefálico , Doença de Fabry/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Testes Neuropsicológicos , Descanso , Adulto Jovem
11.
J Inherit Metab Dis ; 41(1): 141-149, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29039131

RESUMO

Quality of life (QoL) is decreased in patients with Fabry disease (FD). To improve QoL, it is important to understand the influence of FD related characteristics, symptoms, and complications. In this retrospective cohort study we explored the effect of pain (measured by the Brief Pain Inventory), phenotype, treatment, and FD-related complications on QoL. QoL data of Fabry patients as assessed by the EuroQol five dimension questionnaire (EQ-5D) from two international centers of excellence were collected. The aim of this study was to evaluate the effect of sex, phenotype, age, different states of disease severity, pain, and ERT on EQ-5D utilities. For 286 adult FD patients (mean age 42.5 years, 40% men, 60% classical phenotype) 2240 EQ-5Ds were available. QoL is decreased in men as well as women with FD, especially in older men with a classical phenotype. At age 50, utility was lower in men with classical FD compared to those with non-classical disease (ß = -0.12, 95% CI: -0.23 - 0.01, p = 0.037) with further difference in the years thereafter. Cardiovascular complications, stroke or transient ischemic attacks, multiple FD-related complications and pain were also associated with decreased utilities. Overall, no change in utility was seen in patients on ERT over a mean follow-up of 6.1 years. FD leads to a decreased QoL compared to the general population. Disease complications and pain both negatively influence QoL. Adequate assessment and treatment of pain as well as improved strategies to prevent disease complications are needed to improve QoL in the FD population.


Assuntos
Efeitos Psicossociais da Doença , Doença de Fabry/psicologia , Dor/psicologia , Qualidade de Vida , Adulto , Progressão da Doença , Doença de Fabry/diagnóstico , Doença de Fabry/genética , Doença de Fabry/fisiopatologia , Feminino , Humanos , Londres , Masculino , Pessoa de Meia-Idade , Países Baixos , Dor/diagnóstico , Dor/genética , Dor/fisiopatologia , Medição da Dor , Fenótipo , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Inquéritos e Questionários , Fatores de Tempo
12.
J Genet Couns ; 27(1): 217-224, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28799081

RESUMO

The clinical significance of the c.427G>A (p.A143T) variant in GLA is a topic of debate within the lysosomal storage disease community. A review of the literature and published case reports found the clinical impact of the variant to range from classic Fabry symptoms to healthy unaffected males with normal alpha- galactosidase enzyme levels, leaving clinicians unsure of how to manage these individuals. As the number of states testing for Fabry disease on their newborn screening panel has increased, more people with this variant are being identified. The goal of this project was to learn how the uncertainty surrounding the clinical significance of the p.A143T variant affects those with this change. A self-response questionnaire was developed to explore this topic. In addition to evaluating participant feelings, the questionnaire explored individuals' beliefs regarding the pathogenicity of the variant. Results suggest that people have diverse feelings regarding reclassification of the p.A143T variant. Around half of those surveyed reported feeling frustrated by the lack of clear information. Despite the ambiguity regarding the health consequences of this variant, many participants felt that knowing this result helps guide medical management.


Assuntos
Doença de Fabry/psicologia , Testes Genéticos/métodos , alfa-Galactosidase , Adulto , Doença de Fabry/diagnóstico , Doença de Fabry/genética , Feminino , Humanos , Recém-Nascido , Masculino , Mutação , Triagem Neonatal
13.
Mol Genet Metab ; 119(1-2): 109-14, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27591925

RESUMO

Lysosomal storage diseases (LSDs) are an individually rare but collectively common group of hereditary, progressive, multi-systemic disorders. Recent technological advances have brought newborn screening (NBS) for LSDs to attention in the United States. However, many LSD symptoms present in later childhood or adulthood, with a wide spectrum of severity. Because late-onset symptoms stray from the traditional NBS model, healthcare providers have expressed concerns about potential harm to patients and/or their families. In this study, 47 individuals with Fabry disease (FD), 22 with Gaucher disease (GD), and 22 with late-onset Pompe disease (LOPD) were surveyed regarding how their life might have been impacted by NBS. Of the 91 participants, none had symptoms at birth and 42 (46.7%) were symptom-free until adulthood. Over half (52.8%) were diagnosed ≥5years from symptom onset; of these, significantly more had FD (60%) or LOPD (63.6%) than GD (23.8%). However, length of diagnostic odyssey was not significantly correlated with opinion on NBS. Most participants either strongly agreed (45%) or agreed (33.3%) with NBS for their condition, with no significant differences between diseases. Opinions on NBS were correlated with participants' opinions on whether NBS would have resulted in better current health, but uncorrelated with disease severity or current life satisfaction. Significantly more participants with FD (42.6%) and LOPD (63.6%) than GD (13.6%) felt they would have greater life satisfaction had they been diagnosed as a newborn (p=0.007). Almost half (41%) of participants would have made different life decisions, including lifestyle, financial, and reproductive decisions. Regarding potential harm, participants were most concerned about insurability and least concerned about removal of children's autonomy. In conclusion, NBS is highly approved of among individuals with LSDs themselves, as it would significantly eliminate diagnostic odysseys and potentially alter life planning.


Assuntos
Doença de Fabry/epidemiologia , Doença de Gaucher/epidemiologia , Doença de Depósito de Glicogênio Tipo II/epidemiologia , Doenças por Armazenamento dos Lisossomos/epidemiologia , Triagem Neonatal/psicologia , Adolescente , Adulto , Idade de Início , Criança , Pré-Escolar , Doença de Fabry/patologia , Doença de Fabry/psicologia , Feminino , Doença de Gaucher/patologia , Doença de Gaucher/psicologia , Doença de Depósito de Glicogênio Tipo II/patologia , Doença de Depósito de Glicogênio Tipo II/psicologia , Humanos , Recém-Nascido , Doenças por Armazenamento dos Lisossomos/patologia , Doenças por Armazenamento dos Lisossomos/psicologia , Masculino , Pessoa de Meia-Idade , Triagem Neonatal/ética , Pacientes/psicologia
14.
J Genet Couns ; 25(5): 1085-92, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-26948256

RESUMO

Little is known about the experiences of women with Fabry disease. The aim of this study was to explore women's experiences of being heterozygous for Fabry disease. We used an explorative qualitative study design and selected ten Norwegian women who were known heterozygous for Fabry disease to participate. We conducted in-depth semi-structured interviews and analyzed the interviews using inductive thematic analysis. We found that learning about one's heterozygous status may be devastating for some. However, for most of the participants, heterozygous status, as well as doctors' acceptance of symptoms in women heterozygous for Fabry disease, provided an explanation and relief. Although many women did not consider themselves ill, they wished to be acknowledged as more than "just carriers." The participants were grateful for enzyme replacement therapy, although it had its burdens regarding time, planning, and absences from school or work. Women with Fabry disease felt that the lack of knowledge among healthcare professionals about Fabry disease was frustrating and worrisome. These findings suggest that healthcare professionals should acknowledge the different ways women react to their diagnosis, and be aware of the personal costs of receiving treatment.


Assuntos
Doença de Fabry/psicologia , Heterozigoto , Adulto , Idoso , Doença de Fabry/genética , Feminino , Aconselhamento Genético , Humanos , Pessoa de Meia-Idade , Noruega , Pesquisa Qualitativa , Inquéritos e Questionários , Adulto Jovem
15.
Am J Med Genet B Neuropsychiatr Genet ; 168B(3): 204-10, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25739920

RESUMO

Fabry disease (FD) is an X-linked lysosomal storage disorder that results in progressive multisystemic organ complications. Several studies have examined neurocognitive impairments in adults; however, there is a paucity of research examining neurocognitive functioning in children with FD. This is the first exploratory study to examine the neurocognitive functioning of pediatric patients with FD and to evaluate the effects of enzyme replacement therapy (ERT) on neurocognitive functioning within this population. Families attending a national conference with at least one child with FD and one parent affected by FD comprised the sample (n = 48; 24 pediatric patients, 24 parents). Pediatric participants (10 males, 14 females) between the ages of 6 and 18 years and their parent(s) were involved in the study. Data from a demographic questionnaire and two neurocognitive self-report and parent-report measures were analyzed. Parent reports of neurocognitive functioning were also compared to a sample of children with and without head injury and to a sample of children who had undergone liver transplant (LT). Children with FD had poorer cognitive and executive functioning than healthy peers, and were comparable to children with head injury and LT. In addition, children using ERT had higher scores on measures of overall cognitive functioning, as well as fewer problems with attention/working memory and executive functioning. Results of this study suggest that children with FD may exhibit poorer cognitive and executive functioning relative to healthy peers. The use of ERT may mitigate the negative impact of FD on neurocognitive functioning in pediatric patients.


Assuntos
Transtornos Cognitivos/etiologia , Transtornos Cognitivos/psicologia , Função Executiva/fisiologia , Doença de Fabry/complicações , Doença de Fabry/psicologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Testes Neuropsicológicos , Prognóstico , Adulto Jovem
16.
BMC Nephrol ; 15: 188, 2014 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-25432518

RESUMO

BACKGROUND: Impairments of health related quality of life (HRQoL) are frequently observed in Fabry disease (FD) and are known to be related to neuropathic pain and cardiovascular events. This study aimed to explore the role of chronic kidney disease (CKD) in a large cohort of patients with FD. METHODS: In 96 patients (53% female; age 40±12 yrs) with genetically proven FD, HRQoL was assessed by the Medical Outcomes Study (SF-36) questionnaire. All patients were naïve to enzyme replacement therapy. Three categories for kidney dysfunction were chosen, eGFR≥/<60 ml/min/1.73 m2 or need of renal replacement therapy (RRT). Minor (e.g. arrhythmia, angina pectoris, etc.) and major (e.g. myocardial infarction, coronary artery bypass, stroke or implantable cardioverter-defibrillator) vascular events as well as pain and pain therapy were considered in linear regression analyses with the dimensions of HRQoL. RESULTS: Ten patients (10%) had impaired kidney function and a further nine were on RRT (9.4%). Kidney function and pain emerged as the main factors associated with lower scores on the SF 36, in particular on physical components (PCS beta-coefficients for CKD -6.2, for RRT -11.8, for pain -9.1, p<0.05, respectively), while controlling for gender, vascular event and pain-therapy. Relationships were found for mental aspects of HRQoL. Age and history of vascular events were not related to HRQoL. CONCLUSION: Cardiovascular events and pain are important factors related to HRQoL, social functioning and depression. Our study highlights impaired chronic kidney disease, in particular after initiation of RRT, as a strong determinant of reduced HRQoL in FD.


Assuntos
Doença de Fabry/complicações , Qualidade de Vida , Insuficiência Renal Crônica/complicações , Adulto , Doenças Cardiovasculares/complicações , Depressão/etiologia , Progressão da Doença , Doença de Fabry/psicologia , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Neuralgia/complicações , Insuficiência Renal Crônica/terapia , Terapia de Substituição Renal , Fatores de Risco , Inquéritos e Questionários , Adulto Jovem
17.
Arch Clin Neuropsychol ; 29(7): 642-50, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25319043

RESUMO

Fabry disease is an X-linked lysosomal storage disorder which can result in renal, cardiac, and cerebrovascular disease. Patients are at increased risk of stroke and neuroimaging studies note cerebrovascular pathology. This study provides a cognitive profile of a cohort of individuals with Fabry disease and investigates the impact of pain, age, renal, cardiac, and cerebrovascular functioning on cognition and psychological functioning. Seventeen Fabry patients (12 males) with ages ranging 25 to 60 years (M = 46.6+11.8), and 15 age-matched healthy controls (M = 46.2+12.7) were administered a comprehensive neuropsychological battery. Fabry males demonstrated slower speed of information processing, reduced performance on measures of executive functions (verbal generation, reasoning, problem solving, perseveration), were more likely to show clinically significant reductions, and were more likely to report symptoms of anxiety and depression. Conversely, Fabry females performed at a similar level to controls. Correlational analyses indicated a link between cognitive and clinical measures of disease severity.


Assuntos
Transtornos Cognitivos/diagnóstico , Função Executiva/fisiologia , Doença de Fabry/complicações , Desempenho Psicomotor/fisiologia , Adulto , Ansiedade/psicologia , Transtornos Cognitivos/etiologia , Depressão/psicologia , Doença de Fabry/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Índice de Gravidade de Doença , Fatores Sexuais , Estresse Psicológico/psicologia
18.
J Inherit Metab Dis ; 37(2): 177-87, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23949010

RESUMO

BACKGROUND: Fabry disease, an X-linked lysosomal storage disorder, leads to multi-organ dysfunction, including cerebrovascular disease and psychological disorders. However, the prevalence and pattern of associated cognitive dysfunction is not well understood. OBJECTIVES: To investigate whether there is reliable evidence for neuropsychological impairment in patients with Fabry disease and which cognitive domains are affected. To estimate the prevalence of and factors associated with depression in patients with Fabry disease. METHOD: Qualitative systematic review of the literature of studies conducting neuropsychological assessment or measuring the prevalence of depression in adults with Fabry disease using the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines where appropriate. RESULTS: There is some evidence for neuropsychological impairment in Fabry disease in executive functioning, information processing speed and attention, with preservation of: general intellectual functioning, memory, naming, perceptual functioning and global cognitive functioning. Prevalence rates of depression in Fabry disease ranged from 15% to 62%, with the largest study to date reporting a prevalence rate of 46%. The most common factor associated with depression was neuropathic pain, both directly and indirectly by affecting social and adaptive functioning. CONCLUSION: Our review suggests that Fabry disease may be associated with a characteristic pattern of cognitive deficits and a high prevalence of psychological disorders such as depression but highlights the limited available data. Exploring the nature of cognitive impairment in Fabry disease using standardised neuropsychological assessment, brain imaging and measures of depression is an important task for future research.


Assuntos
Transtornos Cognitivos/etiologia , Depressão/etiologia , Doença de Fabry/psicologia , Adulto , Transtornos Cognitivos/diagnóstico , Depressão/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Prevalência , Adulto Jovem
19.
Health Qual Life Outcomes ; 10: 116, 2012 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-22992222

RESUMO

INTRODUCTION: Common symptoms for children with Anderson-Fabry Disease (FD) such as acroparaesthesia and gastrointestinal manifestations can only be objectively assessed in patients using a valid instrument. To date, no such instrument exists. METHODS: A preliminary 40-item measure of symptoms and experience with FD, the Fabry-specific Paediatric Health and Pain Questionnaire (FPHPQ) was developed, but lacked a formal assessment of its measurement properties. The FPHPQ was used in the Fabry Outcome Survey (FOS), a registry for all patients with a confirmed diagnosis of FD who are receiving agalsidase alfa, or are treatment naïve and who are managed by physicians participating in FOS. After an item analysis to explore how items performed and combined into domains, a battery of psychometric analyses was performed to assess the measurement properties of this new instrument. RESULTS: Eighty-seven children (ages 4-18 years) completed the questionnaire. Twenty-three items in three subscales of the questionnaire emerged: pain associated with heat or exertion, pain associated with cold, and abdominal pain and fatigue symptoms. Internal consistency reliability for all three subscales was good (Cronbach alpha ≥ 0.84). Reliability was equally high for all age groups (4-7, 8-12, and 13-18). Test-retest reliability was high for all three subscales (intraclass correlation coefficient ≥ 0.74). Construct validity was demonstrated by moderate correlation with brief pain inventory (BPI), KINDL, and EQ-5D. Known group validity showed all subscales were able to discriminate between Fabry disease severity groups as classified by above or below median of the FOS MSSI (Mainz Severity Score Index) grade. The heat or exertion subscale was responsive to change in symptoms between responders and non-responders as defined by change in EQ-5D index scores between the first and second visit. CONCLUSIONS: Preliminary results indicate that the measurement properties of FPHPQ are valid and reliable for assessing patient-reported symptoms of FD. The questionnaire could be a useful tool for clinicians to understand the progression of disease and monitor treatment effects. FPHPQ will be further validated and refined as the FOS registry is continuously adding more patients.


Assuntos
Doença de Fabry/psicologia , Medição da Dor , Qualidade de Vida , Inquéritos e Questionários/normas , Adolescente , Criança , Pré-Escolar , Doença de Fabry/diagnóstico , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Índice de Gravidade de Doença
20.
Mol Genet Metab ; 104(3): 308-13, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21802328

RESUMO

Little is known on the impact of growing up with Fabry disease (FD) on psychosocial development. Children with FD may suffer from severe recurrent pains in hands and feet, gastro-intestinal symptoms and heat intolerance. These symptoms may influence quality of life and may interfere with a normal psychosocial development. It is important to evaluate psychosocial outcomes of patients with FD into adulthood to be able to optimize support of children with FD. The current cross-sectional questionnaire study investigated psychosocial development and quality of life of 28 young adults with FD, aged 18-35 years (9 males, 19 females), using the Course of Life questionnaire and the Short Form-36 questionnaire for quality of life. The results were compared with an age-matched normative population. We found significant differences in the achievement of milestones in social development of male Fabry patients. The milestones that were affected were 'going out to bars' and 'participation in sports activities'. Other than that FD patients appear to be able to achieve a rather normal psychosocial development until adulthood. Quality of life was decreased in Fabry males in the domains of physical functioning and bodily pain and of general health perception in females.


Assuntos
Desenvolvimento Infantil , Doença de Fabry/fisiopatologia , Doença de Fabry/psicologia , Qualidade de Vida , Comportamento Social , Adolescente , Adulto , Albuminúria/patologia , Análise de Variância , Angioceratoma/patologia , Encéfalo/patologia , Criança , Terapia de Reposição de Enzimas , Doença de Fabry/sangue , Doença de Fabry/complicações , Doença de Fabry/tratamento farmacológico , Feminino , Humanos , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/patologia , Imageamento por Ressonância Magnética , Masculino , Países Baixos , Parestesia/patologia , Albumina Sérica , Estatísticas não Paramétricas , Inquéritos e Questionários
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