Rethinking fatigue in Gaucher disease

Zion, Yehudit Chen; Pappadopulos, Elizabeth; Wajnrajch, Michael; Sandberg, David E.; Rosenbaum, Hanna

doi:10.1016/j.ymgme.2013.12.055

Cited by 5 publications

(9 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the one hand, GD is an autosomal recessive disorder with an annual incidence of about 1/60,000 in the general population (http://www.orpha.net/; (Ferraz et al, ; Nagral, ; Zion, Pappadopulos, Wajnrajch, & Rosenbaum, ). According to clinical features and the extent of central nervous system involvement, three types of GD have been classified.…”

Section: Introductionmentioning

confidence: 99%

Impact of lysosomal storage disorders on biology of mesenchymal stem cells: Evidences from in vitro silencing of glucocerebrosidase (GBA) and alpha‐galactosidase A (GLA) enzymes

Squillaro

Antonucci

Alessio

et al. 2017

Journal Cellular Physiology

View full text Add to dashboard Cite

Lysosomal storage disorders (LDS) comprise a group of rare multisystemic diseases resulting from inherited gene mutations that impair lysosomal homeostasis. The most common LSDs, Gaucher disease (GD), and Fabry disease (FD) are caused by deficiencies in the lysosomal glucocerebrosidase (GBA) and alpha-galactosidase A (GLA) enzymes, respectively. Given the systemic nature of enzyme deficiency, we hypothesized that the stem cell compartment of GD and FD patients might be also affected. Among stem cells, mesenchymal stem cells (MSCs) are a commonly investigated population given their role in hematopoiesis and the homeostatic maintenance of many organs and tissues. Since the impairment of MSC functions could pose profound consequences on body physiology, we evaluated whether GBA and GLA silencing could affect the biology of MSCs isolated from bone marrow and amniotic fluid. Those cell populations were chosen given the former's key role in organ physiology and the latter's intriguing potential as an alternative stem cell model for human genetic disease. Our results revealed that GBA and GLA deficiencies prompted cell cycle arrest along with the impairment of autophagic flux and an increase of apoptotic and senescent cell percentages. Moreover, an increase in ataxia-telangiectasia-mutated staining 1 hr after oxidative stress induction and a return to basal level at 48 hr, along with persistent gamma-H2AX staining, indicated that MSCs properly activated DNA repair signaling, though some damages remained unrepaired. Our data therefore suggest that MSCs with reduced GBA or GLA activity are prone to apoptosis and senescence due to impaired autophagy and DNA repair capacity.

show abstract

Section: Introductionmentioning

confidence: 99%

Impact of lysosomal storage disorders on biology of mesenchymal stem cells: Evidences from in vitro silencing of glucocerebrosidase (GBA) and alpha‐galactosidase A (GLA) enzymes

Squillaro

Antonucci

Alessio

et al. 2017

Journal Cellular Physiology

View full text Add to dashboard Cite

show abstract

“…In addition to a low platelet count, a clotting factor deficiency has also been described, which may contribute to the tendency for bleeding (19) . Patients with Gaucher disease, in addition to depicting hematological disorders, bone and visceral manifestations, may present chronic fatigue as a consequence of hematological disorders (20) . Data from the present study are similar to those previously found, in which approximately 26.4% of the sample reported fatigue and/or lack of energy and 7.7% presented increased active bleeding in tissue injury.…”

Section: Chart 1 (Concluded)mentioning

confidence: 99%

“…The neurological picture is severe, with multiple seizures, hypertonia, apnea and progressive mental retardation. The evolution is rapid, with death in the first two years of life, usually due to pulmonary involvement (17)(18)(19)(20)(21) . Type 3 -Patients with type 3 (chronic neuropathic form) are mostly children and adolescents, with impairment of brain, spleen, liver and bones.…”

Section: Chart 1 (Concluded)mentioning

confidence: 99%

“…The evolution of the neurological picture is variable, but less severe than that of type 2. Survival occurs until the second or third decade of life (17)(18)(19)(20)(21) . Considering the sample studied, the most prevalent signs and symptoms were: epilepsy (10.98%), mental retardation (8.79%) and hypertonia (8.79%), thereby identifying patients with types 2 and 3.…”

Section: Chart 1 (Concluded)mentioning

confidence: 99%

See 1 more Smart Citation

Signs and symptoms in Gaucher Disease: priority nursing diagnoses

2018

View full text Add to dashboard Cite

Objective: Identify the signs and symptoms of patients with Gaucher Disease, inferring possible priority nursing diagnoses. Method: Cross-sectional study, developed in a specialized laboratory, between 2013 and 2015. The sample (n = 91) comprised the records of patients with genetic diagnosis for Gaucher Disease. The study respected research norms. Results: Prevalence of female sex (57.1%), age at diagnosis between 0 and 10 years, and origin from the Southeast Region of Brazil were prevalent. Hematologic changes, bone pain, hepatomegaly, splenomegaly, and fatigue were the most recurrent signs and symptoms. The inferred diagnoses for the studied population were: Risk for bleeding; Fatigue; Chronic pain and Acute pain; Impaired physical mobility; Imbalanced nutrition: less than body requirements; and Risk for Developmental Delay. Conclusion: The establishment of Priority Nursing Diagnoses based on signs and symptoms makes it possible to achieve expected outcomes for each individual in the care context. Descriptors: Gaucher Disease; Cerebrosid Liposidosis Syndrome; Signs and Symptoms; Nursing Process; Nursing Diagnosis. RESUMO Objetivo: Identifi car os sinais e sintomas de pacientes com Doença de Gaucher, inferindo os possíveis diagnósticos de enfermagem prioritários. Método: Estudo transversal, desenvolvido em laboratório especializado, entre 2013 e 2015. A amostra (n=91) foi constituída dos registros de pacientes com diagnóstico genético para Doença de Gaucher. O estudo respeitou normas de pesquisa. Resultados: Foram prevalentes o sexo feminino (57,1%), faixa etária ao diagnóstico entre 0 e 10 anos e proveniência da Região Sudeste do Brasil. Alterações hematológicas, dor óssea, hepatomegalia, esplenomegalia, cansaço foram os sinais e sintomas mais recorrentes. Os diagnósticos inferidos para a população estudada foram: Risco de sangramento; Fadiga; Dor crônica e Dor aguda; Mobilidade física prejudicada; Nutrição desequilibrada: menos do que as necessidades corporais; e Risco de Desenvolvimento atrasado. Conclusão: O estabelecimento dos Diagnósticos de Enfermagem prioritários a partir dos sinais e sintomas possibilita alcançar resultados esperados a cada indivíduo no contexto do cuidado. Descritores: Doença de Gaucher; Síndrome de Liposidose por Cerebrosídeos; Sinais e Sintomas; Processo de Enfermagem; Diagnóstico de Enfermagem. RESUMENObjetivo: Identifi car las señales y los síntomas de pacientes con Enfermedad de Gaucher, infi riendo los posibles diagnósticos prioritarios de enfermería. Método: Estudio transversal, desarrollado entre 2013 y 2015 en un laboratorio especializado. La muestra (n=91) estaba constituida por los registros de pacientes con diagnóstico genético de la Enfermedad de Gaucher. El estudio respetó las normas de la investigación. Resultados: Prevaleció el sexo femenino (57,1%), con franja de edad entre 0 y 10 años y procedencia de la Región Sureste de Brasil. Las alteraciones hematológicas, el dolor óseo, la hepatomegalia, la esplenomegalia y el cansancio fueron las señales y los síntom...

show abstract

“…This is important because wide discrepancies between GD response outcomes that are significant for patients and those most valued by physicians have been described. 2 G D, an autosomal recessive hereditary disorder, is caused by deficient lysosomal acid-glucocerebrosidase activity. Its primary substrate, glucocerebroside (glucosylceramide) is one of the molecular building blocks of complex glycosphingolipids that are physiologically important constituents of cell membranes and receptor complexes.…”

mentioning

confidence: 99%

Encore! Oral therapy for type 1 Gaucher disease

Weinreb

2017

Blood

View full text Add to dashboard Cite

Rethinking fatigue in Gaucher disease

Cited by 5 publications

References 40 publications

Impact of lysosomal storage disorders on biology of mesenchymal stem cells: Evidences from in vitro silencing of glucocerebrosidase (GBA) and alpha‐galactosidase A (GLA) enzymes

Impact of lysosomal storage disorders on biology of mesenchymal stem cells: Evidences from in vitro silencing of glucocerebrosidase (GBA) and alpha‐galactosidase A (GLA) enzymes

Signs and symptoms in Gaucher Disease: priority nursing diagnoses

Encore! Oral therapy for type 1 Gaucher disease

Contact Info

Product

Resources

About