Mucolipidosis type

Mucolipin, also known as mucolipin 1 or mucolipidin (encoded by the MCOLN1 gene), is a TRP channel-related membrane protein, most probably residing in intracellular membranes. Is defective in mucolipidosis type IV disease, a developmental neurodegenerative disorder characterized by lysosomal storage disorder and abnormal endocytosis of lipids. The fimction of mucolipin is unknown. 

Mucolipidosis type 11 (I-cell disease) Mucolipidosis type IIIA (pseudo-Hurler s)... 

For disorders characterized by an underlying enzyme deficiency (e.g., Gaucher disease, Fabry disease, Tay-Sachs, Hurler syndrome), assays of enzyme activity in blood and/or tissues is generally available (Meikle et al., 2004). Mutation analysis is also available, particularly for populations in whom the common disease alleles are known (e.g., mutations among Ashkenazi Jews for Gaucher, Tay-Sachs, Niemann-Pick type A, and mucolipidosis type IV Ostrer, 2001). In other cases, analysis of the gene defect responsible for rare subtypes is available through specialized laboratories. 

Bonifacino IS, Lippincott-Schwartz J. Coat proteins shaping membrane transport. Nat. Rev. Mol. Cell Biol. 2003 4 409 14. LaPlante JM, Sun M, Falardeau J, Dai D, Brown EM, Slau-genhaupt SA, Vassilev PM. Lysosomal exocytosis is unpaired in mucolipidosis type IV. Mol. Genet. Metab. 2006 89 339-348. 

Chen CS, Bach G, Pagano RE. Abnormal transport along the 163. lysosomal pathway in mucolipidosis, type IV disease. Proc. Natl. 

Robinson C, Baker N, Noble J, et al. (2002). The osteodystrophy of mucolipidosis type III and the effects of intravenous pamidronate treatment. J Inherit Metab Dis 25 681-693. 

The preparation of a sodium (4-methylumbelliferyl Of-D-iV-acetylneuraminate) substrate and its use in a sensitive fluorimetric assay of neuraminidase from human leucocytes, Vibrio cholerae, and cultured fibroblasts have been reported. The fibroblast and leucocyte neuraminidases showed maximum activity at pH4.2-4.4 and values of 0.13 and 0.22 mM, respectively the enzyme activity was considerably reduced in cultured fibroblasts of patients with mucolipidosis types I, II, and III. V. cholerae neuraminidase (pH optimum 4.6, 1.5 mM) showed activation by calcium chloride, H4edta, sodium... 

Greene AA, Jonas AJ, Harms E, Smith ML, Pellet OL, Bump EA, Miller AL, Schneider JA. Lysosomal cystine storage in cystinosis and mucolipidosis type II. Pediatr Res 1985 19 1170-1174... 

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...

Falik-Zaccai TC, Zeigler M, Bargal R, et al. Mucolipidosis III type C first-trimester biochemical and molecular prenatal diagnosis. Prenat Diagn 23 211-214,2003. 

By cell fusion and a new single cell hydrolase assay technique, the complementation was observed between mucolipidosis II and two other hereditary lysosomal 3-D-galactosidase-deficient disorders in humans Gj j-gangliosidosis type II and /3-D-galactosidase deficient-type mucolipidosis. The possible mechanisms with which abnormal ML-II jS-D-galactosidase was modified and normalized by the other two different cell strains were discussed. 

In addition to these two types of sialidosis, there are patients with a combined defect of neuraminidase and p-galactosidase (Wenger etal. 1978, Andria etal. 1978, OK.ADAetal. 1979), possibly caused by a common defect in the biosynthetic processing of the two enzymes (Hoogeveen etal. 1980). A neuraminidase deficiency has also been observed in patients with mucolipidosis II (I-cell disease) and mucolipidosis III (Strecker etal. 1976, Thomas etal. 1976). In these disorders, however, the neuraminidase deficiency is but one of many lysosomal hydrolase deficiencies, presumably due to a defect in the proper compart-mentalization of these enzymes (Neufeld 1974). 

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