GM2 gangliosidosis AB variant

Objective: To determine the clinical features and biochemical basis of the first Japanese patient with the GM2 gangliosidosis AB variant. Methods: The clinical manifestations and laboratory findings in the patient were investigated. Cultured fibroblasts from the patient were analyzed by means of immunofluorescence staining with an anti-GM2 ganglioside monoclonal antibody and thin-layer chromatography and immunostaining. GM1 ganglioside catabolism in cultured cells was analyzed by pulse labeling, and the amount of GM2 activator in cells was determined by Western blot analysis. Gene analysis was performed according to standard protocols. Results: The patient showed progressive neurologic manifestations of quite early onset. Muscular weakness and hypotonia became evident by 1 month of age, and the patient then developed a startle reaction, severe psychomotor retardation, and myoclonic seizures. Immunocytochemical analysis clearly revealed the accumulation of GM2 ganglioside in cultured fibroblasts from the patient, and thin-layer chromatography confirmed it. Western blot and metabolic studies showed a complete deficiency of GM2 activator. Gene analysis did not reveal any mutations in the protein coding region of the GM2 activator gene. Conclusion: The clinical features and biochemical basis of this Japanese patient with GM2 gangliosidosis AB variant were determined. Immunocytochemical analysis using cultured fibroblasts as samples is available for the diagnosis of this disease.

[1]  U. Schepers,et al.  Molecular analysis of a GM2-activator deficiency in two patients with GM2-gangliosidosis AB variant. , 1996, American journal of human genetics.

[2]  Hidenori Suzuki,et al.  IV(NeuGc28NeuGc)-GgCer Is Restricted to CD4 T Cells Producing Interleukin-2 and a Small Population of Mature Thymocytes in Mice (*) , 1995, The Journal of Biological Chemistry.

[3]  Yoshiyuki Suzuki,et al.  Prenatal diagnosis of GM2-gangliosidosis Immunofluorescence analysis of ganglioside GM2 in cultured amniocytes by confocal laser scanning microscopy , 1993, Brain and Development.

[4]  H. Ozawa,et al.  Generation of one set of monoclonal antibodies specific for b-pathway ganglio-series gangliosides. , 1992, Biochimica et biophysica acta.

[5]  D. Mahuran,et al.  A Cys138-to-Arg substitution in the GM2 activator protein is associated with the AB variant form of GM2 gangliosidosis. , 1992, American journal of human genetics.

[6]  K. Sandhoff,et al.  A mutation in the gene of a glycolipid‐binding protein (GM2 activator) that causes GM2‐gangliosidosis variant AB , 1991, FEBS letters.

[7]  K. Sandhoff,et al.  Characterization of full‐length cDNAs and the gene coding for the human GM2 activator protein , 1991, FEBS letters.

[8]  A. Lamhonwah,et al.  Isolation and expression of a full-length cDNA encoding the human GM2 activator protein. , 1991, Biochemical and biophysical research communications.

[9]  W. Machleidt,et al.  The complete amino-acid sequences of human ganglioside GM2 activator protein and cerebroside sulfate activator protein. , 1990, European journal of biochemistry.

[10]  G. Fleuren,et al.  KRAS codon 12 mutations occur very frequently in pancreatic adenocarcinomas. , 1988, Nucleic acids research.

[11]  G. Schwarzmann,et al.  Incorporation and metabolism of ganglioside GM2 in skin fibroblasts from normal and GM2 gangliosidosis subjects. , 1985, European journal of biochemistry.

[12]  K. Sandhoff,et al.  Mapping of the gene coding for the human GM2 activator protein to chromosome 5 , 1985, Annals of human genetics.

[13]  K. Sandhoff,et al.  Complexing of glycolipids and their transfer between membranes by the activator protein for degradation of lysosomal ganglioside GM2. , 1982, European journal of biochemistry.

[14]  G. Schwarzmann,et al.  A simple and novel method for tritium labeling of gangliosides and other sphingolipids. , 1978, Biochimica et biophysica acta.