Lysosomal storage disorders

Heriditary lysosomal storage disorder with an heterer-ogeneous clinical presentation including mental retardation and skeletal changes. The disease is caused by... 

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. 

Sialin was first identified as the product of the gene defective in sialidosis, a lysosomal storage disorder. The transporter mediates the movement of sialic acid out of lysosomes by coupling to the proton electrochemical gradient across the lysosomal membrane. Unlike the vesicular neurotransmitter transporters which are antiporters, sialin is a sympoiter with sialic acid and protons both moving out of the lysosome. 

Other complex, neutral oligosaccharides that have been fractionated by l.c. techniques include those found in human milk > and in urine from patients with lysosomal-storage disorders. ... 

J.-Q. Fan, Iminosugars as active-site-specific chaperones for the treatment of lysosomal storage disorders, in P. Compain and O. R. Martin, (Eds.), Iminosugars From Synthesis to Therapeutic Applications, Wiley, Chichester, 2007, pp. 225-247. 

The answer is G. The patient s symptoms are consistent with a lysosomal storage disorder of a progressive type. The appearance of features rather late in life encompassing... 

Genetic defects in the degradation of glycoproteins are representative of lysosomal storage disorders. Each disease is caused by a deficiency of a lysosomal hydrolase, accumulation and urinary excretion of substrates, a progressive clinical course and considerable phenotypic variation. These disorders also manifest the clinical symptoms normally associated with genetic mucopolysaccharidoses, namely coarse facies, dysostosis multiplex and/or ocular involvement. 

The selection of biochemical tests is based on the patients clinical history, the suggestions from the physician, and the experience of the laboratory. The clinical biochemical geneticist should be familiar with the clinical presentation of the different lysosomal storage disorders and their subtypes in order to be able to select the most appropriate tests and to interpret the test results. Therefore, it is strongly recommended that the diagnostic work-up of patients with sphingolipidoses be restricted to specialized laboratories with sufficient experience in diagnosing patients with these rare disorders. 

Beck M (2007) New therapeutic options for lysosomal storage disorders enzyme replacement, small molecules and gene therapy. Hum Genet 121 1-22... 

Gieselmann V (1995) Lysosomal storage disorders. Biochim Biophys Acta 1270 103-136... 

Guo Y, He W, Boer AM, Wevers RA, de Bruijn AM, Greener JEM, Hollak CEM, Aerts JMFG, Galjaard H, van Diggelen OP (1995) Elevated plasma chitotriosidase activity in various lysosomal storage disorders. J Inherit Metab Dis 18 717-722... 

Meikle PJ, Dallas JG, Dean CJ, Lang DL, Bockmann M, Whittle AM, Fietz MJ, Simonsen H, Fuller M, Brooks DA, Hopwood JJ (2006) Newborn screening for lysosomal storage disorders. Mol Genet Metab 88 307-314... 

Meikle PJ, Fietz MJ, Hopwood JJ (2004) Diagnosis of lysosomal storage disorders current techniques and future directions. Expert Rev Mol Diagn 4 677-691... 

Meikle PJ, Hopwood J (2003) Lysosomal storage disorders emerging therapeutic options require early diagnosis. Eur J Pediatr 162 S34-S37... 

Meikle PJ, Hopwood JJ, Clague AE, Carey WF (1999) Prevalence of lysosomal storage disorders. JAMA 281 249-254... 

Pinto R, Caseiro C, Lemos M, Lopes L, Fontes A, Ribeiro H, Pinto E, Silva E, Rocha S, Marcao A, Ribeiro I, Lacerda L, Ribeiro G, Amaral O, Sa Miranda MC (2004) Prevalence of lysosomal storage disorders in Portugal. Eur J Hum Genet 12 87-92... 

Scriver CR, Beaudet AL, Sly WS, Valle D, Childs B, Kinzler KW, Vogelstein (2001) The metabolic molecular bases of inherited disease. Vol III Lysosomal storage disorders McGraw-Hill, New York, Chapters 134, 143,144-148, 150, 151, and 153... 

Wraith JE (2002) Lysosomal storage disorders. Semin Neonatol 7 75-83... 

J. J. Hopwood Early detection and effective therapy of lysosomal storage disorders... 

There are over 40 lysosomal storage disorders (LSDs) characterized by the specific enzyme deficiency and accumulated substrate. Pathologies associated with LSDs are multisystemic and variable including CNS, skeletal, cardiovascular, renal, and ocular system involvement. The aggregate incidence is estimated to approach 1 in 7000 live births (Ellinwood et al., 2004). Inheritance for LSDs is primarily autosomal recessive with the exception of two X-linked diseases (Fabry and mucopolysaccharidosis (MPS) II). Treatment for LSDs relies on providing functional enzyme to the lysosomes of affected cells and has traditionally been confined to bone marrow transplantation, and enzyme replacement therapy (ERT). 

Gene therapy progress for lysosomal storage disorders as of 2004... 

---