Lysosomal deficiency diseases

Otterbach, B., and Stoffel, W., 1995, Acid sphingomyelinase-deficient mice mimic the neurovisceral form of human lysosomal storage disease (Niemann-Pick). Cell 81 1053-1061. 

The answer is D. As this patient ages, a variety of skeletal defects and short stature that are consistent with a lysosomal storage disease (mucolipidosis), either I-cell disease or pseudo-Hurler polydystrophy, are developing. Both diseases arise from a deficiency of an enzyme involved in synthesis of the Man-6-P marker on lysosomal enzymes. Such misaddressed proteins are secreted rather than trafficked to the lysosomes. The degradative function of lysosomes is impaired as a result and the organelles tend to accumulate waste products (hence, the term storage disease ). It is these inclusion bodies or dense structures that would be visible by microscopic examination of the patient s cells in a biopsy specimen. 

Idursulfase (Elaprase) is a drug used to treat mucopolysaccharidosis II or Hunter syndrome. It is a lysosomal storage disease caused by iduronate-2-sulfatase deficiency. Idursulfase is a purified form of iduronate-2-sulfatase produced by recombinant DNA technology in a human cell line. The drug provides clinically important benefits to Hunter syndrome patients. After intravenous infusion Idursulfase is eliminated by peptide hydrolysis with an elimination half-life of 45 minutes. The most common adverse events are hypersensitivity reactions, pyrexia, headache and arthralgia. 

Schindler D, Kanzaki T, Desnick RJ (1990) A method for the rapid detection of urinary glycopeptides in alpha-N-acetylgalactosaminidase deficiency and other lysosomal storage diseases. Clin Chim Acta 190 81-91... 

Acid sphingomyelinase is a lysosomal enzyme that catalyzes the breakdown of sphingomyelin to ceramide and phosphoryl-choline.A deficiency of this enzyme leads to lysosomal accumulation of sphingomyelin in patients with Niemann-Pick disease. Recent data indicate that correct intracellular targeting of acid sphingomyelinase to lysosomes is dependent on the mannose 6-phosphate-mediated pathway. Does this imply that the I-cell patient will present with Niemann-Pick symptoms Can I-cell disease be viewed as a constellation of many lysosomal storage diseases ... 

Dehydrogenase Deficiency, Biotinidase Deficiency, and Adrenoleukodystrophy. Catabolism of essential amino acid skeletons is discussed in the chapters Phenylketonuria and HMG-CoA Lyase Deficiency. The chapters Inborn Errors of Urea Synthesis and Neonatal Hyperbilirubinemia discuss the detoxification and excretion of amino acid nitrogen and of heme. The chapter Gaucher Disease provides an illustration of the range of catabolic problems that result in lysosomal storage diseases. Several additional chapters deal with key aspects of intracellular transport of enzymes and metabolic intermediates the targeting of enzymes to lysosomes (I-Cell Disease), receptor-mediated endocytosis (Low-Density Lipoprotein Receptors and Familial Hypercholesterolemia) and the role of ABC transporters in export of cholesterol from the cell (Tangier disease). 

Keywords Enzyme replacement therapy Enzyme deficiency Lysosomal storage disease Substrate reduction therapy... 

Several lysosomal storage diseases result from defective expression of specific glycosidases. The intracellular accumulation of unprocessed carbohydrate substrates leads to aberrant cellular structure and cell death. Thus, deficient or defective hexosaminidase results in either Tay-Sachs or Sandhoff disease [157]. Fucosidosis, another neurovisceral storage disease, is caused by defective a-L-fucosidase expression. 

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