Normomorphic sialidosis in two female adults with severe neurologic disease and without sialyl oligosacchariduria

Harzer, K.; Cantz, Michael; Sewell, A. C.; Dhareshwar, S. S.; Roggendorf, Wolfgang; Heckl, Reiner; Schofer, O.; Thümler, Reiner; Peiffer, J.; Schlote, W.

doi:10.1007/bf00282535

Cited by 26 publications

(16 citation statements)

References 12 publications

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“…Neuraminidase deficiency together with excretion of sialyloligosaccharides in urine were subsequently demonstrated in few patients with similar features [11, 12, 13, 14, 15]. Since 1979, about 15 other confirmed patients have been described [16, 17, 18, 19, 20, 21, 22, 23, 24]. This syndrome is now generally referred to type I sialidosis.…”

Section: Discussionmentioning

confidence: 99%

Type I Sialidosis: A Clinical, Biochemical and Neuroradiological Study

et al. 2000

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We report biochemical, morphological and neuroradiological findings in a 40-year-old woman affected with type I sialidosis. The clinical symptoms, consisting of a cerebellar syndrome, were first noted at the age of 17 years. The macular cherry-red spot was first observed after 23 years of disease. A CT scan performed at 21 years of age showed enlargement of the fourth ventricle. Nuclear magnetic resonance imaging of the brain performed at the age of 40 showed severe atrophy of the cerebellum and pontine region; atrophy of cerebral hemispheres and of the corpus callosum was also observed. We emphasize the prolonged course of illness in this patient, observed over a long period of time. Of particular interest is the neuroradiological study showing our findings both at the beginning of the disease and after 20 years.

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Section: Discussionmentioning

confidence: 99%

Type I Sialidosis: A Clinical, Biochemical and Neuroradiological Study

et al. 2000

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“…[ 14 C]Methylamine intracellular accumulation, an indicator of excessive storage of water-soluble compounds in lysosomes, was studied in cultured fibroblasts, and enzyme assays for α-N-acetyl-neuraminidase and β-galactosidase were conducted in fibroblast homogenates (Kopitz et al 1996;Harzer et al 1986). Formalin-fixed paraffin-embedded tissue specimens obtained at the autopsy were stained with hematoxylin and eosin and periodic acid Schiff (PAS).…”

Section: Methodsmentioning

confidence: 99%

Prenatal diagnosis and fetal pathology in a Turkish family harboring a novel nonsense mutation in the lysosomal α-N-acetyl-neuraminidase (sialidase) gene

et al. 2001

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We report a Turkish family with parental consanguinity and at risk for sialidosis type II, an inherited autosomal recessive disorder caused by lysosomal alpha-N-acetyl-neuraminidase (sialidase, NEU1) deficiency. The proband was a premature male infant that presented with hydrops, hepatomegaly, respiratory distress syndrome, and anemia and that died of respiratory insufficiency 2 months after birth despite intensive care. An abnormally increased [14C]methylamine incorporation and an isolated deficiency of lysosomal alpha-N-acetyl-neuraminidase were found in cultured skin fibroblasts. A previous pregnancy of the mother terminated in a spontaneous abortion in the 13th week of gestation. A successive pregnancy showed hydrops fetalis, and an enzymatic assay of cultured amniotic fluid cells indicated a deficiency of alpha-N-acetyl-neuraminidase. Following pregnancy termination at 20 weeks gestation, light microscopy of fetal tissues revealed classic vacuolation not only in liver, bone marrow, brain, and kidney, but also in endocrine organs such as the thyroid gland, adrenal gland, hypophysis, and testes, and in the thymus. DNA analysis of the family showed that both the proband and the third sibling had a novel homozygous nonsense point mutation at nucleotide 87 in exon 1 of the alpha-N-acetyl-neuraminidase (neu1) gene causing a substitution of tryptophan at codon 29 by a termination codon (W29X). DNA sequencing of polymerase chain reaction products identified the parents as heterozygous carriers. To detect neu1 mRNA expression, a real-time reverse transcription/polymerase chain reaction was performed, and similar rates of neu1 mRNA expression were found in the fibroblasts of the fetus, the 2nd sibling, and in controls. The very early termination codon with complete loss of neuraminidase activity is probably the molecular basis of the unusually severe vacuolation pattern in this form of congenital sialidosis.

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“…Sialidase activity towards the synthetic substrate 4-MeUmbNeuAc was assayed by the method of Harzer et al [24].…”

Section: Methodsmentioning

confidence: 99%

Partial Characterization and Enrichment of a Membrane‐Bound Sialidase Specific for Gangliosides from Human Brain Tissue

Kopitz

Sinz

Brossmer

et al. 1997

European Journal of Biochemistry

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Gangliosides, constituents of surfaces of vertebrate cells, modulate important cellular functions. Ganglioside-specific sialidases that possibly control these processes have been observed in a number of tissues, but their characterization has proved difficult due to their low abundance and lability. Here we describe the partial isolation and characterization of a ganglioside sialidase from human brain grey matter. After membrane extraction with octylglucoside, the enzyme was purified about 1300-fold by ion-exchange, affinity and gel-permeation chromatographies. Although PAGE still showed several protein bands, specific photoaffinity labelling with iodinated S-N-acetyl-9-(4-azidosalicoylamido)-2,9-dideoxy-2,3-didehydroneuraminic acid identified a single polypeptide of 60 kDa likely to contain the active site of the sialidase. In the presence of 0.4 % octylglucoside, the purified sialidase desialylated gangliosides G,,, G,,,,, G,,, and G,,,, but was inactive towards G,,, GM2, colominic acid, sialyl-(a2-3)-lactose, 2-(4-methylumbelliferyl)-neuraminate, or the glycoprotein fetuin. The ganglioside sialidase activity was strongly inhibited by 2-deoxy-2,3-didehydro-N-acetylneuraminic acid, heparin and heparan sulfate. Because of its substrate and inhibitor profiles, the purified enzyme resembles the activity characterized previously in the plasma membrane of human neuroblastoma cells, but is distinct from a lysosomal activity. The purified brain sialidase thus appears to function in the selective desialylation of gangliosides with terminal sialic acid residues.

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Normomorphic sialidosis in two female adults with severe neurologic disease and without sialyl oligosacchariduria

Cited by 26 publications

References 12 publications

Type I Sialidosis: A Clinical, Biochemical and Neuroradiological Study

Type I Sialidosis: A Clinical, Biochemical and Neuroradiological Study

Prenatal diagnosis and fetal pathology in a Turkish family harboring a novel nonsense mutation in the lysosomal α-N-acetyl-neuraminidase (sialidase) gene

Partial Characterization and Enrichment of a Membrane‐Bound Sialidase Specific for Gangliosides from Human Brain Tissue

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