Gangliosidosis

GM2 gangliosidosis (also known as Tay-Sachs disease) is a rare disorder caused by mutations in the gene encoding the lysosomal, heterodimeric ss-hexosaminidase... 

Sano R, Tessitore A, Ingrassia A, d Azzo A (2005) Chemokine-induced recruitment of genetically modified bone marrow cells into the CNS of GMl-gangliosidosis mice corrects neuronal pathology. Blood 106 2259-2268... 

GM1-gangliosidosis, Morquio B GM1-ganglioside galactose-rich fragments of glycoproteins GM1 ganglioside Keratan sulfate... 

Galactosialidosis is characterized by the simultaneous deficiencies of P-galactosidase and a-neuroaminidase. Clinical and pathological manifestations resemble those in GM1 gangliosidosis and like it show a range of severity. The underlying defect involves a protective protein, which stabilizes these two enzymes by a mechanism that is not understood. Curiously, the protective protein is itself a peptidase. The disorder is most common in Japan. The defective gene has been cloned and mutations have been identified. 

Matsuda, J., Suzuki, O., Oshima, A. et al. Chemical chaperone therapy for brain pathology in GM1-gangliosidosis. Proc. Natl Acad. Sci. U.S.A. 100 15912-15917,2003. 

R. F. G. Frohlich, R. H. Fumeaux, D. J. Mahuran, R. Saf, A. E. Stiitz, M. B. Tropak, J. Wicki, S. G. Withers, and T. M. Wrodnigg, 1-Deoxy-D-galactonojirimycins with dansyl capped N-substitu-ents as P-galactosidase inhibitors and potential probes for GMi gangliosidosis affected cell lines, Carbohydr. Res., 346 (2011) 1592-1598. 

Studies on Krabbe s disease and GM 1-gangliosidosis have contributed a great deal to our understanding of the catabolism of glycosphin-... 

Fig. 4.1.9 Electrophoresis pattern of different types of MPS (indicated beneath the corresponding band). Standards (STD) and normal controls (N) were also run on each gel. GAGs are labeled on the left side of the figure. The picture was kindly provided by Dr. E Buerger, Metabolic Center Heidelberg, Germany. GM1 GM1-gangliosidosis, MSD multiple sulfatase deficiency ML II mucolipidosis II, LZ loading zone of the gel...

For cells with /1-galactosidase deficiency (GM1 gangliosidosis or Morquio type as well as I-cell disease), the measured enzyme activity will be significantly lower than the true enzyme activity. In addition, cases of multiple sulfatase deficiency will also show low N-acetylgalactosamine-6-sulfatase activity. Therefore, arylsulfatase A or another sulfatase, as well as /1-galactosidase activities should also be determined in case of suspicious results. To exclude poor sample quality, the determination of a-mannosidase is recommended. 

In most cases, missing jS-galactosidase activity will be associated with GM1-gangliosidosis. The differential diagnosis between GM1-gangliosidosis and Morquio type disease must be based on the clinical evaluation of the patient because the enzymatic activity alone will not be helpful. 

Figure 4.2.2 depicts the urinary oligosaccharide patterns of sialidosis (a-neur-aminidase deficiency), GM1 gangliosidosis and mucopolysaccharidosis type IVB (/3-galaclosidase deficiency) compared to a normal urine and standards of raffinose, lactose and glucose. In patients with sialidosis, a densely staining band close to the... 

Fig. 4.2.2 TLC of urinary oligosaccharides. Left to right standards of raf-finose (lower), lactose (middle) and glucose (upper), sialidosis, GM1 gangliosidosis, mucopolysaccharidosis IVB and a control...

Suzuki Y, Oshima A, Nanba E (2001) /S-Galactosidase deficiency (/ -galactosidosis) GMl gangliosidosis and Morquio disease. In Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The Metabolic and Molecular Bases of Inherited Disease, vol III, 8th edn. McGraw-Hill, New York, pp 3775-3809... 

GM2-gangliosidosis, O-variant, Sandhoff disease 268800 -Hexosaminidase A and (EC 3.2.1.52) L, F, P, D GM2-ganglioside, GA2 (asialio-GM2)-ganglio-side, globoside U (oligosaccharides)... 

This enzyme is deficient in GM2-gangliosidosis, -variant (Tay-Sachs disease Table 4.4.1, Fig. 4.4.1). The assay is based on the method described by Inui and Wenger [23]. 

This enzyme is increased in Gaucher disease and may also be increased, but to a lesser extent, in other sphingolipidoses such as Niemann-Pick disease type A/ and NPC, Krabbe disease, and GM1-gangliosidosis. The assay is based on the method described by Hollak et al. [22] and Guo et al. [17]. 

Chamoles NA, Blanco MB, Iocansky S, Gaggioli D, Specola N, Casentini C (2001) Retrospective diagnosis of GM1 gangliosidosis by use of a newborn-screening card. Clin Chem 47 2068... 

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