RESUMO
BACKGROUND: Gaucher disease (GD) is caused by deficiency of beta-glucocerebrosidase (GCase) due to biallelic variations in the GBA1 gene. Parkinson's disease (PD) is the second most common neurodegenerative condition. The classic motor symptoms of PD may be preceded by many non-motor symptoms (NMS), which include hyposmia, rapid eye movement (REM) sleep behavior disorder, constipation, cognitive impairment, and depression. Population studies have identified mutations in GBA1 as the main risk factor for idiopathic PD. The present study sought to evaluate the prevalence of NMS in a cohort of patients with GD type 1 from Southern Brazil. METHODOLOGY: This is an observational, cross-sectional study, with a convenience sampling strategy. Cognition was evaluated by the Montreal Cognitive assessment (MoCa), daytime sleepiness by the Epworth Scale, depression by the Beck Inventory, constipation by the Unified Multiple System Atrophy Rating Scale, and REM sleep behavior disorder by the Single-Question Screen; hyposmia by the Sniffin' Sticks. Motor symptoms were assessed with part III of the Unified Parkinson's Disease Rating Scale. All patients were also genotyped for the GBA1 3'-UTR SNP (rs708606). RESULTS: Twenty-three patients (female = 13; on enzyme replacement therapy = 21, substrate reduction therapy = 2) with a mean age of 41.45 ± 15.3 years (range, 22-67) were included. Eight patients were found to be heterozygous for the 3'-UTR SNP (rs708606). Fourteen patients (8 over age 40 years) presented at least one NMS; daytime sleepiness was the most frequent (n = 10). Two patients (aged 63 and 64, respectively) also presented motor symptoms, probably drug-related. CONCLUSIONS: NMS were prevalent in this cohort. We highlight the importance of a multidisciplinary follow-up focusing on earlier diagnosis of PD, especially for patients with GD type 1 over the age of 40.
Assuntos
Doença de Gaucher/diagnóstico , Doença de Gaucher/fisiopatologia , Doença de Parkinson/diagnóstico , Doença de Parkinson/fisiopatologia , Adulto , Idoso , Brasil , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/fisiopatologia , Estudos Transversais , Feminino , Glucosilceramidase/genética , Glucosilceramidase/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Transtorno do Comportamento do Sono REM/diagnóstico , Transtorno do Comportamento do Sono REM/fisiopatologia , Inquéritos e QuestionáriosRESUMO
Common forms of Parkinson's disease have long been described as idiopathic, with no single penetrant genetic factor capable of influencing disease aetiology. Recent genetic studies indicate a clear association of variants within several lysosomal genes as risk factors for idiopathic Parkinson's disease. The emergence of novel variants suggest that the aetiology of idiopathic Parkinson's disease may be explained by the interaction of several partially penetrant mutations that, while seemingly complex, all appear to converge on cellular clearance pathways. These newly evolving data are consistent with mechanistic studies linking α-synuclein toxicity to lysosomal abnormalities, and indicate that idiopathic Parkinson's disease resembles features of Mendelian lysosomal storage disorders at a genetic and biochemical level. These findings offer novel pathways to exploit for the development of disease-altering therapies for idiopathic Parkinson's disease that target specific components of the lysosomal system.
Assuntos
Doenças por Armazenamento dos Lisossomos/fisiopatologia , Doença de Parkinson/etiologia , Doença de Parkinson/fisiopatologia , Doença de Gaucher/genética , Doença de Gaucher/fisiopatologia , Humanos , Doenças por Armazenamento dos Lisossomos/genética , Lisossomos/genética , Lisossomos/fisiologia , Mitocôndrias/patologia , Doença de Parkinson/genética , Fatores de Risco , alfa-Sinucleína/metabolismoRESUMO
INTRODUCTION: Gaucher disease (GD) is characterized by clinical heterogeneity and is associated with metabolic abnormalities such as increased resting energy expenditure. OBJECTIVES: To assess the basal metabolic rate (BMR) of patients with GD type I followed at the Gaucher Disease Reference Center of Rio Grande do Sul, Brazil. PATIENTS AND METHODS: Fourteen patients (male=6) and 14 healthy controls matched by gender, age and body mass index (BMI) were included in the study. The nutritional status of patients was assessed by BMI. The BMR was measured by indirect calorimetry. In two patients, it was possible to perform BMR in the pre- and the post-treatment periods. RESULTS: Mean age and BMI of patients and controls were, respectively, 32.8 ± 17.6 and 32.1 ± 16.6 years and 23.3 ± 3.1 and 22.4 ± 3.1 kg/m(2). Twelve patients were receiving enzyme replacement therapy (ERT) with imiglucerase (mean duration of treatment=5.2 ± 4.3 years; mean dosage of imiglucerase=24.2 ± 7.3 UI/kg/inf). Five patients (36%) were overweight, and nine (64%) were normal weight. Mean BMR of patients on ERT was 27.1% higher than that of controls (p=0.007). There was no difference between the BMR of patients on ERT and not on ERT (n=4) (p=0.92). Comparing the BMR of patients on ERT and their controls with the BMR estimated by the Harris-Benedict equation, the BMR of patients was 6.3% higher than the estimated (p = 0.1), while the BMR of their controls was 17.0% lower than the estimated (p = 0.001). CONCLUSION: Most treated GD type I patients were normal weight. The patients including those on ERT showed higher BMR when compared to controls. Imiglucerase is probably unable to normalize the hypermetabolism presented by GD type I patients. Additional studies should be performed to confirm our findings.
Assuntos
Metabolismo Basal , Doença de Gaucher/metabolismo , Adolescente , Adulto , Peso Corporal/fisiologia , Brasil , Estudos de Casos e Controles , Feminino , Doença de Gaucher/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemAssuntos
Doença de Gaucher/fisiopatologia , Doença de Gaucher/genética , Humanos , Lactente , Masculino , FenótipoRESUMO
Se presenta el caso de un paciente de 17 años de edad, con enfermedad de Gaucher tipo 1, cuya evolución data desde los cinco años de edad, manifestada por aumento de volumen abdominal a expensas de hepatomegalia y esplenomegalia masiva, con hipodesarrollo corporal y sexual, así como hiperesplenismo, anemia, trombocitopenia y lesiones óseas. El diagnóstico se integró con datos clínicos, radiológicos e histopatológicos
Assuntos
Humanos , Masculino , Adolescente , Doença de Gaucher , Doença de Gaucher/diagnóstico , Doença de Gaucher/patologia , Doença de Gaucher/fisiopatologia , Hepatomegalia/etiologia , Hiperesplenismo , Esplenomegalia/etiologiaRESUMO
Partial splenectomy was introduced to achieve the benefits of splenectomy and to avoid the risk of overwhelming infection in patients with symptomatic Gaucher disease. We observed regrowth of the splenic remnant, reemergence of preoperative symptoms, and new bone involvement among most of our patients who had undergone partial splenectomy. Enzyme replacement therapy has markedly limited indications for splenectomy, partial or total, for Gaucher disease.
Assuntos
Doença de Gaucher/cirurgia , Esplenectomia , Adolescente , Adulto , Doenças Ósseas/etiologia , Criança , Feminino , Seguimentos , Doença de Gaucher/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Osteonecrose/etiologia , Baço/crescimento & desenvolvimento , Resultado do TratamentoRESUMO
Os autores fazem revisao bibliográfica sobre a Doença de Gaucher, uma rara patologia, tecendo comentários sobre sua forma de apresentaçao, fisiopatologia, manifestaçoes clínicas, diagnóstico e tratamento.
Assuntos
Humanos , Lactente , Pré-Escolar , Criança , Adolescente , Adulto , Doença de Gaucher/fisiopatologia , Esplenectomia , Doença de Gaucher/classificação , Doença de Gaucher/diagnóstico , Doença de Gaucher/terapiaRESUMO
Portal hypertension in Gaucher disease is unusual; the seventh known patient with this complication is reported. Prior to portacaval shunting in this child, a localized obstruction of the inferior vena cava at the subdiaphragmatic level was demonstrated by caval manometry and inferior vena cavography. At autopsy, centrilobular hepatic fibrosis seemed to be responsible for the portal hypertension. Nodular enlargement of the right and caudate lobes of the liver was the cause of the caval obstruction; elevated caval resistance may have contributed to the portal hypertension and possibly was responsible for failure of a portacaval anastomosis. The value of preoperative inferior vena cavography in addition to arterial portography in children with portal hypertension is stressed.