Deficient hexosaminidase activity in an exceptional case of Tay-Sachs disease with additional storage of kidney globoside in visceral organs

Sandhoff, Konrad; Andreae, U.; Jatzkewitz, Horst

doi:10.1016/0024-3205(68)90024-6

Cited by 286 publications

(91 citation statements)

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“…distintos; las subunidades & y p de la HEX A y la c. La variante AB de la gangli~sidosis GM2 proteina activadora GM2. Un defecto en alguno resulta de un defecto en el cromosorna 5, en de los tres genes puede deteriorar el el gen que codifica para la proteina catabolismo del gangliósido (2)(3)(4)(5)(6)(7)(8) (10)(11)(12)(13)(14). salina 0.85%: la liberación de las enzimas se realizó por sonicación y se analizó el sobrePara la determinación de HEX, se han descrito técnicas electroforéticas que emplean el sustrato sintético 4-metilumbelliferil 2-acetamida 2 Se ensayaron diferentes tiempos de sonicación, deoxi p-D-glucopiranósido.…”

Section: Discussionunclassified

Determinación de la actividad enzimática de la hexosaminidasa en fluidos biológicos

et al. 1996

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ResumenEste estudio describe un método electroforético que emplea el sustrato fluorogénico 4-metilumbelliferil 2-acetamida 2-deoxi-O-D-glucopiranosido, para la determinación enzimática de la hexosaminidasa (HEX) en linfocitos de sangre periférica, líquido amniótico, suero y orina. Se propone que la electroforésis sirva como método confirmatorio del diagnóstico de la gangliosidosis GM2, ya que permite determinar la actividad enzimática de la HEX y hacer la diferenciación de las isoenzimas (HEX A y HEX 8). La deficiencia de estas isoenzimas se detecta por disminución o ausencia de fluorescencia. SummaryThis study describes a method, that uses electrophoresis for the enzyme hexosaminidase (HEX), the substrate 4-metil-umbelliferyl 2-acetamide 2-deoxi-beta-Dglucopiranoside. We used samples from serum, urine and amniotic fluid, frorn normal people. We propose this method could be used as diagnostic for gangliosidoses GM2, because of the sensibility for the detection of isoenzymes HEX A and HEX B, and the capability to detect differences in fluorescence.La hexosaminidasa (HEX) pertenece a la familia enfermedad poseen actividad de HEX A de las hidrolasas: esta enzima está rese ente en deficiente. oero. la HEX B es normal (2. 3. 9). . se presenta una mutación en el gen La degradación lisosomal de la p-N-(cromosoma 5) que codifica para la acetilgalactosamina terminal del gangliósido subunidad P Estos pacientes tiene deficien-te GM2 requiere tres polipéptidos genéticamente actividad de HEX A y B (2, 3, 9).. . distintos; las subunidades & y p de la HEX A y la c. La variante AB de la gangli~sidosis GM2 proteina activadora GM2. Un defecto en alguno resulta de un defecto en el cromosorna 5, en de los tres genes puede deteriorar el el gen que codifica para la proteina catabolismo del gangliósido (2-8).activadora. Estos ~acientes tienen activa la Se presentan tres tipos de gangliosidosis GM2:HEX A y HEX B, pero, el catabolismo de a. Enfermedad de Tay-Sachs o variante B; GM2 es deficiente (2, 3, 9).causada por una mutación en el cromosoma Hasta el momento, se han encontrado más de 15, en el locus que codifica para la subunidad cuarenta mutaciones alélicas diferentes en el loa de la HEX A. Los individuos con esta cus de la subunidad a como responsables de

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Section: Discussionunclassified

Determinación de la actividad enzimática de la hexosaminidasa en fluidos biológicos

et al. 1996

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“…b) Separation of A and B isozymes on DEAEcellulose [2]. c) Affinity chromatography on Sepharose-bound ligand 2-acetoamido-N-(s-amino-caproyl)-2-deoxy b-…”

Section: Enzymevmentioning

confidence: 99%

“…There are several inherited disorders, manifested mainly as lipid storage diseases, which are characterized by the absence of either one or both of hexosaminidase isozymes, e.g. Sandhoff s disease, in which both isozymes are missing [2] and Tay-Sachs disease, in which only the basic isozyme, B, is present [ 3 ] . The conclusion about the absence of hexosaminidase A in Tay-Sachs tissues was drawn both from the absence of enzymic activity in the electrophoretic region corresponding to hexosaminidase A and from Enzyme.…”

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confidence: 99%

Specific Determination of N‐Acetyl‐β‐d‐hexosaminidase Isozymes A and B by Radioimmunoassay and Radial Immunodiffusion

Geiger

Navon

Ben‐Yoseph

et al. 1975

European Journal of Biochemistry

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The two major isozymes of N-acetylhexosaminidase, namely hexosaminidases A and B were quantitatively determined in tissues and biological fluids of both normal individuals and Tay-Sachs patients. The determination was carried out by two sensitive immunoassays : radial immunodiffusion, using chromogenic substrate, and radioimmunoassay, which were developed in this study. For this pupose we used either a cross-reactive antiserum which reacts to a similar extent with both isozymes, or an antiserum reacting exclusively with hexosaminidase A (obtained by selective immunoadsorption). This enabled the quantitisation of the two isozymes separately, or in the presence of each other, in purified enzyme preparations or in tissue homogenates, affording a direct positive determination of hexosaminidase A. The results demonstrated that normal tissues contain the two isozymes in comparable amounts, whereas tissues of Tay-Sachs patients lack hexosaminidase A or any material which carries the A-specific antigenic determinants. The possible applications of these assays and their potential use in diagnosis are discussed.

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“…The accumulation of ganglioside GM2 in the tissues of patients with Tay-Sachs disease appears to be due to the absence of hexosaminidase A, the elevated levels of hexosaminidase B being unable to hydrolyse the storage product [7] . By analogy with Sanfillipo syndrome type B in which the lack of N-acetylaglucosaminidase results in the storage of heparan North-Holland Publishing Company -Amsterdam sulphate [8] the almost complete absence of N-acetyl-/3-hexosaminidase in Sandhoffs disease [9] might be expected to result In the storage of those glycosaminoglycans containing the /J-N-acetylhexosaminide linkage. It is generally agreed, however, that there is no storage of glycosaminoglycans [ IO,1 l] in Tay-Sachs disease or Sandhoff s disease.…”

Section: Introductionmentioning

confidence: 99%

Human N‐acetyl‐β‐hexosaminidases: Hydrolysis of N,N′diacetylchitobiose by a low molecular weight enzyme

Stirling¹

1974

FEBS Letters

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Deficient hexosaminidase activity in an exceptional case of Tay-Sachs disease with additional storage of kidney globoside in visceral organs

Cited by 286 publications

References 5 publications

Determinación de la actividad enzimática de la hexosaminidasa en fluidos biológicos

Determinación de la actividad enzimática de la hexosaminidasa en fluidos biológicos

Specific Determination of N‐Acetyl‐β‐d‐hexosaminidase Isozymes A and B by Radioimmunoassay and Radial Immunodiffusion

Human N‐acetyl‐β‐hexosaminidases: Hydrolysis of N,N′diacetylchitobiose by a low molecular weight enzyme

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