1/19. Enzyme studies in GM2 gangliosidiosis, and their application in prenatal diagnosis.Assay of hexosaminidase a and B enzymes in four cases with developmental regression and cherry red spot on fundus examination confirmed that three cases had tay-sachs disease, and one case had sandhoff disease. prenatal diagnosis was carried out by hexosaminidase enzyme assay in amniotic fluid and cells in one family, and chorionic villus sample in the second family. The fetus was diagnosed to be unaffected in one, and affected in the other family. Assay of hexosaminidase a and B is useful for specific diagnosis of GM2 gangliosidosis, and for prenatal diagnosis to reduce the burden of these disorders.- - - - - - - - - - ranking = 1keywords = enzyme (Clic here for more details about this article) |
2/19. Compound heterozygosity with two novel mutations in the HEXB gene produces adult sandhoff disease presenting as a motor neuron disease phenotype.Little information is available on molecular defects involved in adult sandhoff disease presenting as motor neuron disease phenotype. We studied enzyme activities of beta-hexosaminidase (Hex) and the HEXB gene encoding the beta-subunit of Hex in a family of the Japanese case. Enzyme assay with 4-methylumbelliferyl-2-acetamido-2-deoxy-beta-D-glucopyranoside revealed a reduction in Hex A and B activity in proband's leukocytes. Although the activity of both in the mother were intermediate between those of controls and the proband, only Hex B reduction determined with heat inactivation was found in the father. Analysis of HEXB gene demonstrated two novel point mutations. The first mutation, IVS2-1G>A, was located at the 3'-splice acceptor site of intron 2 derived from the mother, causing exon 3 skipping. The resultant mRNA encoded a shorter beta-chain, which may not form an active enzyme. The second mutation was a G-to-A transition in exon 13 (c.1598G>A) derived from the father and resulted in arginine-to-histidine substitution at amino acid position 533 (R533H). Expression of R533H mutation in COS-1 cells demonstrated a lack of normal Hex activity, indicating that this mutation is pathological. Compound heterozygosity of these two mutations may trigger the development of adult sandhoff disease with a motor neuron disease phenotype.- - - - - - - - - - ranking = 1keywords = enzyme (Clic here for more details about this article) |
3/19. Infantile Sandhoff's disease: multivoxel magnetic resonance spectrosecopy findings.Sandhoff's disease is a rare, genetic lysosomal storage disease leading to delayed myelination or demyelination. Although neuroimaging findings in this disease have been reported previously, magnetic resonance spectroscopy findings have not been reported. In this report, we present magnetic resonance imaging and magnetic resonance spectrscopy features of two cases with Sandhoff's disease. magnetic resonance spectroscopy revealed findings indicating widespread demyelination in both cases and neuroaxonal loss and anaerobic metabolism in the second case. magnetic resonance spectroscopy could provide useful information in the explanation of the clinical picture of cases with Sandhoff's disease.- - - - - - - - - - ranking = 345.90282722807keywords = lysosomal storage, storage, storage disease (Clic here for more details about this article) |
4/19. Juvenile sandhoff disease--nine new cases and a review of the literature.Juvenile sandhoff disease (McKusick 268800) is a rare lysosomal storage disorder with only 12 cases recorded in the literature. This condition is also referred to as the subacute form of hexosaminidase deficiency. We describe 9 new cases of Pakistani origin and compare these with the other published cases. ataxia and speech abnormalities were the commonest presentation. constipation and urinary incontinence were frequent and may be due to autonomic neuropathy. Cherry-red spot was not noted in any of our cases. Increased lower limb reflexes were the commonest physical finding. Significant delay in diagnosis may be due to the nonspecific presentation of this condition. Diagnosis was on the basis of hexosaminidase deficiency. Residual enzyme activity did not correlate with the clinical picture. Emerging therapies make early diagnosis of this disorder important.- - - - - - - - - - ranking = 342.48971995719keywords = lysosomal storage, storage, enzyme (Clic here for more details about this article) |
5/19. A new N-acetyl-beta-D-hexosaminidase disease with late onset of progressive neurological symptoms.Clinical data are presented on a 30-year-old male with normal early development (4-5 years) but subsequent progressive impairment of psychomotor functions. He has marked kyphoscoliosis and talipes calcaneo-valgus. The organs appear normal and the patient can walk unaided and feed himself although he does not recognize his parents. He has normal fundi oculi. Biochemical data show an absence of mucopolysacchariduria and very low but detectable levels of N-acetyl-beta-D-hexosaminidase in serum and leucocytes. The clinical symptoms are much milder than would normally be expected from such a profound enzyme deficiency (sandhoff disease).- - - - - - - - - - ranking = 0.5keywords = enzyme (Clic here for more details about this article) |
6/19. A case refort of sandhoff disease.sandhoff disease is a rare autosomal recessive metabolic disease presenting bilateral optic atrophy and a cherry red spot in the macula. This case report presents the characteristics of a patient with sandhoff disease as assessed by ophthalmic, neuroimaging, and laboratory procedures. Ophthalmologic examination revealed that the patient could not fixate her eyes on objects nor follow moving targets. A pale optic disc and a cherry red spot in the macula were seen in both eyes. Low signal intensity at the thalamus and high signal intensity at the cerebral white matter were noted in a T2-weighted brain MR image. A lysosomal enzyme assay using fibroblasts showed the marked reduction of both total beta-hexosaminidases, A and B. Based on the above clinical manifestations and laboratory findings, we diagnosed the patient as having sandhoff disease.- - - - - - - - - - ranking = 453.1844038214keywords = lysosomal enzyme, enzyme (Clic here for more details about this article) |
7/19. GM2-gangliosidosis. Clinical and biochemical aspects of four cases.We discuss four cases of GM2-gangliosidosis. In one of them the biochemical diagnostic confirmation was difficult. This case revealed striking discrepancies between the results of different methods of enzyme assay. The hexosaminidase a determination based on pH inactivation is not always reliable; assay with natural substrate may be necessary. However, the results with the newly developed substrate 4-MU-GlcNac-6-SO4 are promising and it seems to be a good alternative to the traditional (pH or heat) inactivation procedures. The deficiency can be shown in leukocytes, plasma and fibroblasts with the 6-sulfated substrate. The carrier state seems better reflected in plasma hexosaminidase a than in leukocyte hexaminidase A levels.- - - - - - - - - - ranking = 0.5keywords = enzyme (Clic here for more details about this article) |
8/19. A case of combined Farber and sandhoff disease.We describe a patient with the biochemically established combination of Farber and sandhoff disease. A 6-month-old girl of consanguineous Turkish parents presented with hoarseness, stridor, scattered skin nodules, painful swelling of hand joints and ankles, and cherry-red macular spots. Until the age of 2 years her motor and physical condition deteriorated distinctly, however her mental state remained unchanged. A biopsied skin nodule disclosed lysosomal inclusions within storage cells that were typical of Farber disease (curved tubular structures). However, other inclusions (e.g. zebra bodies) were also found. Biochemical findings included ceramide accumulation in skin nodules and cultured fibroblasts, impaired ceramide degradation on loading of cultured fibroblasts with radioactive sphingomyelin, profoundly decreased ceramidase activity in fibroblasts as well as total beta-hexosaminidase activity in fibroblasts and serum, absent hexosaminidase a and B bands on cellogel zymograms, increased urinary oligosaccharide excretion of the sandhoff disease type, and a partial reduction of ceramidase and total beta-hexosaminidase activities in fibroblasts from her father. A diagnosis of combined Farber and sandhoff disease was made. The effect of both enzyme deficiencies on the clinical manifestations in this patient and the genetic basis of this combination require further studies.- - - - - - - - - - ranking = 5.1446143385831keywords = storage, enzyme (Clic here for more details about this article) |
9/19. Ganglioside storage, hexosaminidase lability, and urinary oligosaccharides in adult Sandhoff's disease.Two adult sisters with severe spinocerebellar degeneration were deficient in hexosaminidase a and B. GM2 ganglioside storage in brain tissue obtained by autopsy from one patient was most pronounced in the cerebellum. Hexosaminidase activity in brain tissue was negligible, but fibroblasts from the second patient contained relatively high amounts of heat-labile activities of both isoenzymes. pulse-chase experiments showed synthesis of precursor alpha- and beta-chains of hexosaminidase, maturation of the alpha-chain, but only a very small amount of mature beta-chain. These data indicate a destabilizing mutation in the beta-locus. Substrate-specific effects of this mutation were demonstrated by the urinary oligosaccharide pattern.- - - - - - - - - - ranking = 23.723071692916keywords = storage, enzyme (Clic here for more details about this article) |
10/19. First trimester prenatal diagnosis of Sandhoff's disease.Chorionic villus sampling was performed on two patients with a previous family history of Sandhoff's disease. Total beta-hexosaminidase (Hex) activity in case 1 was within the normal range (case 1: 6365 mumol/h/g protein; control range: 3227-24 495 mumol/h/g protein). The beta-hexosaminidase isoenzyme pattern was found to be normal. These results were confirmed on cultured amniotic fluid cells. In case 2, the total Hex activity was 672 mumol/h/g protein, i.e., 7 per cent of the control mean (10,085 mumol/h/g protein), and chromatography demonstrated that more than 50 per cent of this activity was due to the abnormal isoenzyme beta-hexosaminidase S (Hex S). The fetus was predicted to be affected by Sandhoff's disease and this was confirmed on fetal tissues after termination of pregnancy. This study demonstrates that a fetus affected by Sandhoff's disease can be reliably diagnosed during the first trimester of pregnancy.- - - - - - - - - - ranking = 1keywords = enzyme (Clic here for more details about this article) |
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