Lysosomal deficiency

Type II Pompe s disease Deficiency of lysosomal a-1 4- and 1 ->6-glucosldase (acid maltase) Fatal, accumulation of glycogen in lyso-somes, heart failure. 

Man 6-P receptors, located in the Golgi apparatus, bind the Man 6-P residue of these enzymes and direct them to the lysosomes. Fibroblasts from patients with I-cell disease (see below) are severely deficient in the activity of the GIcNAc phosphotransferase. 

Genetic Deficiencies of Glycoprotein Lysosomal Hydrolases Cause Diseases Such as a-Mannosidosis... 

The GAGs are synthesized by the sequential actions of a battery of specific enzymes (glycosyltransferases, epimerases, suhotransferases, etc) and are degraded by the sequential action of lysosomal hydrolases. Genetic deficiencies of the latter result in mucopolysaccharidoses (eg, Hurler syndrome). 

Nadler, H. L. and Egan, T. J. "Deficiency of Lysosomal Acid Phosphatase a New Familial Metabolic Disorder". 

Aldurazyme (tradename, also known as laronidase) is a recombinant version of one polymorphic variant of the human enzyme a-L-iduronidase. It was approved for general medical use in the USA in 2003 and is indicated for the treatment of patients with certain forms of the rare inherited disease MPS I. MPS I is caused by a deficiency of a lysosomal a-L-iduronidase, which normally catalyses the hydrolysis of terminal a-L-iduronic acid residues from the glycosaminoglycans dermatan sulfate and heparin sulfate. The deficiency results in accumulation of the glycosaminoglycans throughout the body, causing widespread cell and tissue dysfunction. 

Other leukodystrophies are associated with the lysosomal and peroxisomal disorders in which specific lipids or other substances accumulate due to a deficiency in a catabolic enzyme - for example Krabbe s disease, meta-chromatic leukodystrophy (MLD) and adrenoleuko-dystrophy (ALD) [1,2]. (These are discussed in detail in Ch. 40.) Similarly, disorders of amino acid metabolism can lead to hypomyelination - for example phenylketonuria and Canavan s disease (spongy degeneration) [1, 2, 25] (Ch. 40). The composition of myelin in the genetically... 

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