Biochemical characterization of β‐hexosaminidase in different biological specimens from eleven patients with GM2‐gangliosidosis B1 variant

Ribeiro, Maria Gil; Pinto, Rui; Santos, Rosário; Maia, Maria; Sá-Miranda, Clara

doi:10.1007/bf01799940

Cited by 8 publications

(1 citation statement)

References 11 publications

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“…1,16 This mutation has a wide ranging geographic and ethnic distribution, 16,17 although it has a particularly high incidence in northern Portugal, [18][19][20] and it has been suggested that it may have originated in this region. 16,18 In the Portuguese population as a whole, the prevalence of the B1 variant has been estimated as 0.84 per 100.000 live births, although this rate is nearly double for the northern part of the country.…”

Section: Discussionmentioning

confidence: 99%

Thermodynamic Determination of Plasma and Leukocyte beta-Hexosaminidase Isoenzymes in Homozygote and Heterozygote Carriers for the GM2 Gangliosidosis B1 Variant

Casal¹,

Pérez²,

Tutor³

2003

Am J Clin Pathol

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In the GM2 gangliosidosis B1 variant, the mutated isoenzyme A of beta-hexosaminidase (Hex) is incapable of hydrolyzing ganglioside GM2 and negatively charged substrates. Biochemical characterization of this lysosomal disease is carried out using synthetic alpha-subunit-specific sulfated substrates, as heat-inactivation assays are not applicable. The apparent enzyme activation energy of Hex using the chromogenic substrate 3,3'-dichlorophenolsulfonphthaleinyl N-acetyl-beta-D-glucosaminide is related directly to the relative proportions of Hex A and Hex B isoenzymes. This thermodynamic variable was used for the study of Hex enzyme heterogeneity in 3 patients with the GM2 gangliosidosis B1 variant and 6 heterozygote carriers. Hex activity was determined at 25 degrees C, 30 degrees C, 35 degrees C, and 37 degrees C in a Cobas Bio analyzer (Roche Diagnostics, Basel, Switzerland), and Arrhenius plot slopes and apparent activation energies were calculated in plasma samples and mononuclear and polymorphonuclear leukocyte lysates. The determination of the Hex isoenzymes in plasma presented a high discrimination power for B1 variant patients but not for heterozygote carriers, in whom false-negative results may be obtained. However, thermodynamic evaluation of the isoenzyme composition of Hex in leukocyte lysates permits the biochemical identification of patients with the GM2 gangliosidosis B1 variant and of heterozygote carriers.

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Section: Discussionmentioning

confidence: 99%

Thermodynamic Determination of Plasma and Leukocyte beta-Hexosaminidase Isoenzymes in Homozygote and Heterozygote Carriers for the GM2 Gangliosidosis B1 Variant

Casal¹,

Pérez²,

Tutor³

2003

Am J Clin Pathol

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Prenatal diagnosis of GM₂‐gangliosidosis B1 variant

et al. 1995

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Prenatal diagnosis in a pregnancy at risk for a juvenile B1 variant of GM2-gangliosidosis was carried out. The biochemical study of the cultured amniocytes and the affected fetal brain is reported. The results obtained show that the sulphated artificial substrate can be used in the diagnosis of B1 variant, but not the neutral one. The accumulation of GM2-ganglioside in the fetal brain of the B1 juvenile form and an infantile form of GM2-gangliosidosis (0 variant) was compared.

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Identification of GM2‐gangliosidosis B1 variant carriers

Ribeiro¹,

Pinto²,

Oliveira

et al. 1993

J of Inher Metab Disea

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GM2-gangliosidosis B1 variant, considered a rare disorder with a wide geographical and ethnic distribution, appears to be exceptionally frequent in Portugal. In order to establish a carrier detection method for this disease we have determined the ratio of enzymatic activities against 4MUGS and 4MUG in urine from B1 variant obligate carriers and controls, using the total extract and the Hex A immunobound to a monoclonal antibody. The Hex A immunoassay was applied to the identification of carriers in B1 variant families and the results obtained were compared with those from DNA analysis. The reliability and feasibility of the Hex A immunoassay make it a suitable method for B1 variant carrier screening, which is particularly important for the prevention of this severe neurological disease in the population at risk.

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Biochemical characterization of β‐hexosaminidase in different biological specimens from eleven patients with GM2‐gangliosidosis B1 variant

Cited by 8 publications

References 11 publications

Thermodynamic Determination of Plasma and Leukocyte beta-Hexosaminidase Isoenzymes in Homozygote and Heterozygote Carriers for the GM2 Gangliosidosis B1 Variant

Thermodynamic Determination of Plasma and Leukocyte beta-Hexosaminidase Isoenzymes in Homozygote and Heterozygote Carriers for the GM2 Gangliosidosis B1 Variant

Prenatal diagnosis of GM₂‐gangliosidosis B1 variant

Identification of GM2‐gangliosidosis B1 variant carriers

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Biochemical characterization of β‐hexosaminidase in different biological specimens from eleven patients with GM2‐gangliosidosis B1 variant

Cited by 8 publications

References 11 publications

Thermodynamic Determination of Plasma and Leukocyte beta-Hexosaminidase Isoenzymes in Homozygote and Heterozygote Carriers for the GM2 Gangliosidosis B1 Variant

Thermodynamic Determination of Plasma and Leukocyte beta-Hexosaminidase Isoenzymes in Homozygote and Heterozygote Carriers for the GM2 Gangliosidosis B1 Variant

Prenatal diagnosis of GM2‐gangliosidosis B1 variant

Identification of GM2‐gangliosidosis B1 variant carriers

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Product

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Prenatal diagnosis of GM₂‐gangliosidosis B1 variant