Tay-Sachs screening: motives for participating and knowledge of genetics and probability.
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A highly-educated, socially aware group of persons presented themselves for Tay-Sachs screening having learned about it mainly from friends, newspapers, radio, and television but not from physicians or rabbis. After learning that screening was possible and deciding that it is in principle a good idea, and after discussing it with relatives and friends but not with physicians and rabbis, they presented themselves for the test. Although the participants knew that Tay-Sachs is a serious disease and that Jews are vulnerable, few of them knew much about the genetics of the disease, its frequency, or the incidence of the carrier state. This experience of screening for Tay-Sachs carriers suggests the need for physicians to learn the relation of genetics to preventive medicine, and for the public to learn more about the biology of man. (+info)
Tay-Sachs screening: social and psychological impact.
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Participants in two Tay-Sachs screening programs were generally satisifed with the organization of the tests and the results. There was no evidence of adverse impact on reproductive plans or interpersonal relations, and the respondents professed to believe in the value of screening. While the carriers discussed their condition freely with others and were no less favorable to the idea of screening than the noncarriers, about one-half of their number expressed discomfort in being told they were heterozygotes. These feelings were allayed by counseling, but there was evidence of some residual unease. It is suggested that this anxiety would be less prominent and more easily reduced if screening were done under conditions of ordinary primary medical care rather than outside the conventional system. (+info)
Matrix-assisted laser desorption ionization time-of-flight mass spectrometric analysis of glycosphingolipids including gangliosides.
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Long chain base compositions of gangliosides containing mainly stearic acid could be determined without any chemical modification by matrix-assisted laser desorption ionization time-of-flight mass spectrometry with delayed ion extraction (DE MALDI-TOF MS). The analytical results for the long chain base compositions of various samples of GM1 from the brain tissues of patients with different diseases at different ages confirmed that the proportion of d20:1 (icosasphingosine) and d20 (icosa-sphinganine) of the total sphingosine bases increased quickly until adolescent or adult age and then remained constant slightly exceeding 50%; this value was evidently higher than the proportion of d20:1 and d20 of GM1 in various adult mammalian brains. A long chain base composition of GM1 from the brain tissue of a patient with infantile type of GM1-gangliosidosis at 4y2m was abnormal and so was in two sibling patients with Spielmeyer-Vogt type of juvenile amaurotic idiocy at 19y and 21y in spite of that in the latter there was no accumulation of GM1 in the brain tissue. On the other hand, a patient with adult type of GM1 gangliosidosis at 66y showed a local accumulation of GM1 in the putamen and caudate nucleus, but its long chain base composition was found to be normal. It was of interest that the white matter of Eker rat with hereditary renal carcinoma contained a large amount of plasmalocerebroside as compared with the amount of cerebroside and sphingomyelin. The individual molecular species of plasmalocerebroside were identified by DE MALDI-TOF MS. (+info)
Tay-Sachs' and Sandhoff's diseases: the assignment of genes for hexosaminidase A and B to individual human chromosomes.
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The techniques of somatic cell genetics have been used to establish the linkage relationships of loci coding for two forms (A and B) of hexosaminidase (EC 3.2.1.30; 2-acetamido-2-deoxy-beta-D-glucoside acetamidodeoxyglucohydrolase) and to determine whether a structural relationship exists between these forms. In a series of human-mouse hybrid cell lines, hexosaminidase A and B segregated independently. Our results and those reported by other investigators are used to analyze the proposed structural models for hexosaminidase. We have also been able to establish a syntenic relationship between the gene locus responsible for the expression of hexosaminidase A and those responsible for mannosephosphate isomerase and pyruvate kinase-3 and to assign the gene for hexosaminidase B to chromosome 5 in man. There is thus a linkage between specific human autosomes and enzymes implicated in the production of lipid storage diseases. (+info)
Automated differentiation and measurement of hexosaminidase isoenzymes in biological fluids and its application to pre- and postnatal detection of Tay-Sachs disease.
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Three hexosaminidase (EC 3.2. 1.52) isoenzymes other than isoenzymes A and B in body fluids have been separated by chromatography on diethylaminoethyl cellulose. By inserting a microcolumn into a continuous-flow system for automated, fluorometric hexosaminidase analysis [Clin. Chem. 20, 538 (1974)], samples eluted with buffered-NaCl gradients can be continuously monitored. Isoenzyme patterns were obtained for fluids from normal individuals, pregnant women, Tay-Sachs disease carriers, pregnant carriers, and patients with the disease. These chromatograms revealed a hitherto undetected isoenzyme (I-3) in serum. An increase in serum hexosaminidase isoenzyme I-2 (or P) during pregnancy is characteristic of a carrier pattern. Our data show that serum and urinary hexosaminidase isoenzyme patterns may be used in addition to leukocyte analysis, to distinguish a pregnant carrier from a normal pregnant woman. All fluids tested demonstrated no isoenzyme A activity and above-normal activity of isoenzymes B and (or) I-2 in homozygotes. Urine is preferred fluid for postnatal and amniotic fluid for the prenatal diagnosis of the disease. Quantitative data on isoenzyme A obtained with the procedure described here agree well with those obtained by heat-and pH-inactivation methods. (+info)
Heterogeneity of human hepatic H-acetyl-beta-D-hexosaminidose. A activity toward natural glycosphingolipid substrates.
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A crude soluble preparation of human hepatic N-acetyl-beta-D-hexosaminidase was examined for its activities toward three natural glycosphingolipid substrates after fractionation by the isoelectric focusing procedure. Profiles of activities toward N-acetylgalactosaminyl-galactosyl-glucosylceramide (asialo GM2-ganglioside) and N-acetylgalactosaminyl-galactosyl-galactosyl-glucosylceramide (globoside) were always identical with that of nonspecific N-acetyl-beta-D-hexosaminidase as determined with artificial substrates. The Component A of the enzyme had the activity peak at an isoelectric point of 5.0 to 5.1. In contrast, hydrolytic activities toward N-acetylgalactosaminyl-[N-acetylneuraminyl]galactosyl- glucosylceramide (GM2-ganglioside) were associated with only the most acidic subfraction of the hexosaminidase A component. The activity to hydrolyze GM2-ganglioside had its peak at an isoelectric point of 4.8 to 4.9. These findings might provide an explanation for the GM2-ganglioside accumulation in juvenile GM2-gangliosidosis (partial deficiency of hexosaminidase A) and in the so-called AB variant of GM2-gangliosidosis (apparently normal hexosaminidase A and B activity). (+info)
Above-normal urinary excretion of urinary ceramides in Farber's disease, and characterization of their components by high-performance liquid chromatography.
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We compared the sphingolipid content of urine from a patient with Farber's disease with that of control urine. The ceramides were measured by high-performance liquid chromatography. The patient's urine contained 1.2 mug of ceramides per milligram of creatinine, more than 200-fold the normal amount. The urinary ceramides were isolated by high-performance liquid chromatography for further identification. They contained mainly nonhydroxy fatty acids and only a small quantity of those with 2-hydroxy fatty acids. This contrasts with the previously described composition of the patient's renal and cerebellar tissue. The fatty acid and long-chain base compositions of the urinary ceramides containing nonhydroxy fatty acids were nearly identical to those of the patient's kidney. (+info)
Childhood organic neurological disease presenting as psychiatric disorder.
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Over a period of one year 12 children with complaints which had been diagnosed as due to a psychiatric disorder presented to a paediatric neurological unit where neurological disease was diagnosed. The group was characterized by behavioural symptoms such as deteriorating school performance, visual loss, and postural disturbance, which are unusual in children attending child psychiatric departments. It is suggested that where there is diagnostic uncertainty the presence of these physical symptoms calls for periodic neurological reassessment, and attention is drawn to the rare but serious disorders which may thus be diagnosed. Making an organic diagnosis, however, should not preclude psychosocial management of emotional reactions in these families. (+info)