Correlation among Genotype, Phenotype, and Biochemical Markers in Gaucher Disease: Implications for the Prediction of Disease Severity

Whitfield, Phillip D.; Nelson, Paul V.; Sharp, P.; Bindloss, Colleen A.; Dean, Caroline J.; Ravenscroft, Elaine M.; Fong, B. A.; Fietz, Michael; Hopwood, John J.; Meikle, Peter J.

doi:10.1006/mgme.2001.3269

Cited by 45 publications

(29 citation statements)

References 27 publications

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“…The procedures described in this study are simple to apply and are economically viable for use in clinical analysis laboratories, where equipment required to work with different glycosphingolipids is not always available, such as mass spectrometer (Groener et al, 2007;Whitfield et al, 2002) and HPLC (Ullman, McCluer, 1977). The technology tested in this study can be applied simultaneously to a considerable number of samples.…”

Section: Discussionmentioning

confidence: 99%

Quantification of glucosylceramide in plasma of Gaucher disease patients

Müller

Petry

Vianna

et al. 2010

Braz. J. Pharm. Sci.

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Gaucher disease is a sphingolipidosis that leads to an accumulation of glucosylceramide. The objective of this study was to develop a methodology, based on the extraction, purification and quantification of glucosylceramide from blood plasma, for use in clinical research laboratories. Comparison of the glucosylceramide content in plasma from Gaucher disease patients, submitted to enzyme replacement therapy or otherwise, against that from normal individuals was also carried out. The glucosylceramide, separated from other glycosphingolipids by high performance thin layer chromatography (HPTLC) was chemically developed (CuSO 4 / H 3 PO 4 ) and the respective band confirmed by immunostaining (human anti-glucosylceramide antibody / peroxidase-conjugated secondary antibody). Chromatogram quantification by densitometry demonstrated that the glucosylceramide content in Gaucher disease patients was seventeen times higher than that in normal individuals, and seven times higher than that in patients on enzyme replacement therapy. The results obtained indicate that the methodology established can be used in complementary diagnosis and for treatment monitoring of Gaucher disease patients. Uniterms:Glucosylceramide. Blood plasma analysis. Gaucher disease.A doença de Gaucher é uma esfingolipidose caracterizada pelo acúmulo de glicosilceramida. O objetivo deste estudo foi desenvolver metodologia baseada na extração, purificação e quantificação da glicosilceramida plasmática a qual possa ser usada em laboratórios de pesquisa clínica. Após o desenvolvimento desta metodologia, foi proposto, também, comparar o conteúdo de glicosilceramida presente no plasma de pacientes com doença de Gaucher, submetidos ou não a tratamento, com aquele de indivíduos normais. A glicosilceramida, separada de outros glicoesfingolipídios por cromatografia de camada delgada de alto desempenho (HPTLC), foi revelada quimicamente (CuSO 4 /H 3 PO 4 ) e a respectiva banda foi confirmada por imunorrevelação (anticorpo anti-glicosilceramida humana/anticorpo secundário conjudado à peroxidase). A quantificação do cromatograma por densitometria demonstrou que o conteúdo de glicosilceramida nos pacientes com doença de Gaucher era 17 vezes maior que aquele de indivíduos normais e 7 vezes maior que aquele dos pacientes com doença de Gaucher submetidos a tratamento com terapia de reposição enzimática. Os resultados obtidos demonstram que a metodologia estabelecida pode ser usada como diagnóstico complementar e como monitoração do tratamento de pacientes com doença de Gaucher.Unitermos: Glicosilceramida. Análise plasmática. Doença de Gaucher.

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Section: Discussionmentioning

confidence: 99%

Quantification of glucosylceramide in plasma of Gaucher disease patients

Müller

Petry

Vianna

et al. 2010

Braz. J. Pharm. Sci.

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“…Supernatants were assayed for the presence of rhNS. ␣rhNS polyclonal AB (28) and ␣rhNS-23.B2 monoclonal AB (28) (which recognizes only human sulfamidase and not mouse sulfamidase) were used in a DELFIA immunoquantification assay as described previously (29).…”

Section: Methodsmentioning

confidence: 99%

Enzyme-Replacement Therapy from Birth Delays the Development of Behavior and Learning Problems in Mucopolysaccharidosis Type IIIA Mice

Gliddon

Hopwood

2004

Pediatr Res

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Mucopolysaccharidosis type IIIA (MPS IIIA; Sanfilippo syndrome) is a lysosomal storage disorder characterized by severe CNS degeneration, resulting in behavioral abnormalities and loss of learned abilities. Early treatment is vital to prevent long-term clinical pathology in lysosomal storage disorders. We have used naturally occurring MPS IIIA mice to assess the effects of long-term enzyme-replacement therapy initiated either at birth or at 6 wk of age. MPS IIIA and normal control mice received weekly i.v. injections of 1 mg/kg recombinant human sulfamidase until 20 wk of age. Sulfamidase is able to enter the brain until the blood-brain barrier completely closes at 10 -14 d of age. MPS IIIA mice that were treated from birth demonstrated normal weight, behavioral characteristics, and ability to learn. MPS IIIA mice that were treated from birth performed significantly better in the Morris water maze than MPS IIIA mice that were treated from 6 wk of age or left untreated. A reduction in storage vacuoles in cells of the CNS in MPS IIIA mice that were treated from birth is consistent with the improvements observed. These data suggest that enzyme that enters the brain in the first few weeks of life, before the blood-brain barrier matures, is able to delay the development of behavior and learning difficulties in MPS IIIA mice. , and glucosamine-6-sulfatase (MPS IIID) (1). MPS III has an estimated incidence of 1 in 66,000 births in Australia, with MPS IIIA the most common (2). MPS III is characterized by severe CNS degeneration, resulting in progressive mental retardation. After a period of seemingly normal development, patients exhibit a range of symptoms, including rapid loss of social skills with hyperactivity and aggressive behavior, loss of learning ability, disturbed sleep patterns, hirsutism, coarse facies, and diarrhea. Death occurs in severely affected children in the mid-to late-teenage years usually as a result of respiratory infection (3). Phenotypic variation in MPS III ranges from severe to intermediate to attenuated, a result of heterogeneity at the molecular level. A total of 62 causative mutations have been identified for MPS IIIA (4).A naturally occurring mouse model of MPS IIIA has been described (5), a colony of which is established in Adelaide. Disease in the mice results from a base substitution at codon 31 in the sulfamidase gene, altering an aspartic acid to an asparagine (D31N) (6). This aspartic 31 is involved in binding of the divalent metal ion needed for catalytic function (7-9). MPS IIIA mice exhibit widespread intracellular storage in a variety of cell types. Affected mice are also reported to store secondarily gangliosides G M2 and G M3 , a feature also reported in two MPS IIIA dog models (10,11), a knock-out MPS IIIB mouse (12), and a caprine MPS IIID model (13

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“…Enzim eksikliğinde glukoserebrozid yıkılamadığından retiküloendotelyal sistem hücrelerinin lizozomlarında birikir. Farklı mutant alellerinin mutasyonuna bağlı olarak Gaucher hastalığında farklı klinik tablolar ortaya çıkabilir (2) . Kronik depolanmaya bağlı olarak kemik iliği infiltrasyonu, progresif hepatosplenomegali ve iskelet bulguları gelişir.…”

Section: Discussionunclassified

Gaucher Disease With Respiratuar Distress: A Case Report

Urgancı¹,

Keskin²

2016

Cocuk Dergisi

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Solunum Sıkıntısı ile Başvuran Gaucher HastasıGaucher hastalığı, retiküloendotelyal sistem (RES) hücreleri içinde glukozilseramit birikiminin neden olduğu, lizozomal glukoserobrosidaz enzim eksikliğine bağlı otozomal resesif geçişli bir depo hastalığıdır. Monosit ve makrofaj lizozomlarında biriken glukoserebrosid birçok organı, sıklıkla da kemik iliği, lenf bezleri, karaciğer ve dalağı infiltre eder ve multisistemik bulgulara yol açar. Gaucher hastalığının nörolojik tutulum olup olmaması ve nörolojik hastalığa ilerleme durumuna göre 3 alt tipi bulunmaktadır. Tip 1 erişkin formu olup, nörolojik tutulum görülmez. Tip 2 infantil veya akut nöronopatik tip, Tip 3 juvenil subakut nöronopatik tipidir. Enzim ve gen tedavilerindeki ilerlemeler ile küratif tedavisi gündeme gelen, ender bir genetik bozukluk olan Gaucher hastalığı, kliniğimizde saptanan bu vaka ile birlikte yeniden gözden geçirilmiştir.

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Correlation among Genotype, Phenotype, and Biochemical Markers in Gaucher Disease: Implications for the Prediction of Disease Severity

Cited by 45 publications

References 27 publications

Quantification of glucosylceramide in plasma of Gaucher disease patients

Quantification of glucosylceramide in plasma of Gaucher disease patients

Enzyme-Replacement Therapy from Birth Delays the Development of Behavior and Learning Problems in Mucopolysaccharidosis Type IIIA Mice

Gaucher Disease With Respiratuar Distress: A Case Report

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