Common HEXB polymorphisms reduce serum HexA and HexB enzymatic activities, potentially masking Tay-Sachs disease carrier identification

Vallance, Hilary; Morris, Tara; Coulter‐Mackie, Marion B.; Lim-Steele, Joyce; Kaback, Michael M.

doi:10.1016/j.ymgme.2005.10.012

Cited by 7 publications

(7 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other advantages of this method include the small volume of blood needed, the ease and rapidity of platelet isolation, and the ability to freeze platelets with no apparent loss of activity ([Nakagawa et al, 1977, 1978a], and references therein). While serum enzyme analysis is widely used and may be appropriate in certain situations, the higher rate of inconclusive results compared to the platelet assay makes it less practical in large‐scale screenings where up to hundreds of individuals are tested within a short time frame [Prence et al, 1993; Casal et al, 2005; Vallance et al, 2006]. However, since the cell separation and the column chromatography steps of the platelet assay can be labor intensive (and hence costly) when large numbers of samples are involved, one option is to perform serum screening as the first line test and reflexing to the platelet assay for inconclusive and carrier samples.…”

Section: Discussionmentioning

confidence: 99%

“…As the gene pool of those who identify as Ashkenazi Jewish is diversifying, more individuals will be tested who have some non‐Jewish heritage. HexA enzyme analysis is a well‐tested example of an accurate and reliable screening method that transcends ethnicity and can be used in any population group [Casal et al, 2005; Vallance et al, 2006]. Since more individuals of partial non‐Jewish heritage may undergo testing through these large screening programs, future research should explore whether enzyme analysis may allow for expanded screening programs in non‐Jewish populations.…”

Section: Discussionmentioning

confidence: 99%

“…However, biochemical testing has been available for decades and has the capability of detecting almost all carriers, irrespective of ethnic background [O'Brien et al, 1970; Suzuki et al, 1971; Navon and Padeh, 1972; Carmody et al, 1973; Singer et al, 1973; Saifer et al, 1976; Nakagawa et al, 1978a,b]. The goals of this study were to determine the performance characteristics of clinical TSD testing in current large scale, community‐based screening programs and to determine if molecular testing alone is adequate in light of increasing genetic diversity within the Jewish community [D'Souza et al, 2000; 2000–2001 NJPS report http://www.ujc.org/page.aspx?id=46253; Vallance et al, 2006].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Population‐based Tay‐Sachs screening among Ashkenazi Jewish young adults in the 21st century: Hexosaminidase a enzyme assay is essential for accurate testing

Schneider

Nakagawa

Keep

et al. 2009

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Tay-Sachs disease (TSD) carrier screening, initiated in the 1970s, has reduced the birth-rate of Ashkenazi Jews with TSD worldwide by 90%. Recently, several nationwide programs have been established that provide carrier screening for the updated panel of Jewish genetic diseases on college campuses and in Jewish community settings. The goals of this study were to determine the performance characteristics of clinical TSD testing in college- and community-based screening programs and to determine if molecular testing alone is adequate in those settings. Clinical data for TSD testing were retrospectively anonymized and subsequently analyzed for 1,036 individuals who participated in these programs. The performance characteristics of the serum and the platelet Hexosaminidase assays were compared, and also correlated with the results of targeted DNA analysis. The serum assay identified 29 carriers and the platelet assay identified 35 carriers for carrier rates of 1/36 and 1/29, respectively. One hundred sixty-nine samples (16.3%) were inconclusive by serum assay in marked contrast to four inconclusive samples (0.4%) by the platelet assay. Molecular analysis alone would have missed four of the 35 carriers detected by the platelet assay, yielding a false negative rate of 11.4% with a sensitivity of 88.6%. Based on the results of this study, platelet assay was superior to serum with a minimal inconclusive rate. Due to changing demographics of the Ashkenazi Jewish population, molecular testing alone in the setting of broad-based population screening programs is not sufficient, and biochemical analysis should be the assay of choice.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Population‐based Tay‐Sachs screening among Ashkenazi Jewish young adults in the 21st century: Hexosaminidase a enzyme assay is essential for accurate testing

Schneider

Nakagawa

Keep

et al. 2009

American J of Med Genetics Pt A

View full text Add to dashboard Cite

show abstract

“…Hereditary factors include phenylketonuria, 15 galactosemy, 16 Mowat-Wilson syndrome, 17 Tay-Sachs disease, 18 and glycogen deposit disease, among others. These …”

Section: Hereditary Factorsmentioning

confidence: 99%

Intellectual disability: definition, etiological factors, classification, diagnosis, treatment and prognosis

Katz¹,

Lazcano‐Ponce²

2008

Salud pública Méx

108

View full text Add to dashboard Cite

Intellectual disability: definition, etiological factors, classification, diagnosis, treatment and prognosis.Salud Publica Mex 2008;50 suppl 2:S132-S141. AbstractEtiology and classification: Causal factors related with cognitive disability are multiples and can be classified as follows: Genetic, acquired (congenital and developmental), environmental and sociocultural. Likewise, in relation to the classification, cognitive disability has as a common denominator a subnormal intellectual functioning level; nevertheless, the extent to which an individual is unable to face the demands established by society for the individual's age group has brought about four degrees of severity: Mild, moderate, severe and profound. Diagnostic: The clinical history must put an emphasis on healthcare during the prenatal, perinatal and postnatal period and include the results of all previous studies, including a genealogical tree for at least three generations and an intentional search for family antecedents of mental delay, psychiatric illnesses and congenital abnormalities. The physical exam should focus on secondary abnormalities and congenital malformations, somatometric measurements and neurological and behavioral phenotype evaluations. If it is not feasible to establish a clinical diagnosis, it is necessary to conduct high-resolution cytogenetic studies in addition to metabolic clinical evaluations. In the next step, if no abnormal data are identified, submicroscopic chromosomal disorders are evaluated. Prognosis: Intellectual disability is not curable; and yet, the prognostic in general terms is good when using the emotional wellbeing of the individual as a parameter. Conclusions: Intellectual disability should be treated in a comprehensive manner. Nevertheless, currently, the fundamental task and perhaps the only one that applies is the detection of the limitation and abilities as a function ResumenEtiología y clasificación: múltiples factores causales están relacionados con la discapacidad cognoscitiva y pueden clasificarse de la siguiente manera: genéticos, adquiridos, (congénitos y de desarrollo), ambientales y socioculturales. Del mismo modo, en cuanto a la clasificación, la discapacidad cognoscitiva tiene como común denominador un nivel de funcionamiento intelectual por debajo de lo normal; sin embargo, la medida en que una persona es incapaz de afrontar las demandas establecidas por la sociedad para su grupo de edad ha dado origen a cuatro grados de severidad: ligera, moderada, severa y profunda. Diagnóstico: el historial clínico debe hacer énfasis en el cuidado de la salud durante el periodo prenatal, perinatal y postnatal e incluir los resultados de todos los estudios previos, incluyendo un árbol genealógico de al menos tres generaciones y una búsqueda intencional de antecedentes familiares de retraso mental, enfermedades psiquiátricas y anomalías congénitas. El examen físico debe concentrarse en anomalías secundarias y en malformaciones congénitas, mediciones somatométricas, y evaluaciones del fenotipo neurológico y ...

show abstract

“…When the differential heat inactivation method is employed, total hexosaminidase measured is in the range of 370-1,120 nmol/h/ml [51], with the percentage of Hex A in serum samples 60-77% for noncarriers and 34-54% for carriers, whereas in leukocytes, % Hex A falls in the range of 56-70% for non-carriers and 36-50% for carriers. Frequently, serum from homozygous TSD patients gives values of 2-5% HexA due to thermal denaturation of Hex B [38] 1 .…”

Section: Assays With Fluorogenic and Chromogenic Artificial Substratesmentioning

confidence: 99%

Hexosaminidase assays

Wendeler

Sandhoff

2008

Glycoconj J

View full text Add to dashboard Cite

beta-Hexosaminidases (EC 3.2.1.52) are lysosomal enzymes that remove terminal beta-glycosidically bound N-acetylglucosamine and N-acetylgalactosamine residues from a number of glycoconjugates. Reliable assay systems are particularly important for the diagnosis of a family of lysosomal storage disorders, the GM2 gangliosidoses that result from inherited beta-hexosaminidase deficiency. More recently, aberrant hexosaminidase levels have also been found to be associated with a variety of inflammatory diseases. Apart from patient testing and carrier screening, practical in vitro assays are indispensable for the characterization of knock-out mice with potentially altered hexosaminidase activities, for detailed structure-function studies aimed at elucidating the enzymatic mechanism, and to characterize newly described enzyme variants from other organisms. The purpose of this article is to discuss convenient hexosaminidase assay procedures for these and other applications, using fluorogenic or chromogenic artificial substrates as well as the physiological glycolipid substrate GM2. Attempts are also made to provide an overview of less commonly used alternative techniques and to introduce recent developments enabling high-throughput screening for enzyme inhibitors.

show abstract

Common HEXB polymorphisms reduce serum HexA and HexB enzymatic activities, potentially masking Tay-Sachs disease carrier identification

Cited by 7 publications

References 15 publications

Population‐based Tay‐Sachs screening among Ashkenazi Jewish young adults in the 21st century: Hexosaminidase a enzyme assay is essential for accurate testing

Population‐based Tay‐Sachs screening among Ashkenazi Jewish young adults in the 21st century: Hexosaminidase a enzyme assay is essential for accurate testing

Intellectual disability: definition, etiological factors, classification, diagnosis, treatment and prognosis

Hexosaminidase assays

Contact Info

Product

Resources

About