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Chapter 32 - Lysosomal Storage Disorders in Children
- from Section IV - Metabolic Liver Disease
- Edited by Frederick J. Suchy, Ronald J. Sokol, William F. Balistreri
- Edited in association with Jorge A. Bezerra, Cara L. Mack, Benjamin L. Shneider
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- Book:
- Liver Disease in Children
- Published online:
- 19 January 2021
- Print publication:
- 18 March 2021, pp 570-592
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Summary
Lysosomes are membrane-bound cellular organelles that contain multiple hydrolases needed for the digestion of various macromolecules including mucopolysaccharides, glycosphingolipids, cholesterol esters and oligosaccharides. Moreover, the lysosome is emerging as a central hub for nutrient signaling and autophagy to maintain cellular homeostasis. A schematic of the lysosomal system enzyme trafficking and substrate accumulation is shown in Figure 32.1. The lysosomal storage diseases are a group of over 50 diseases that are characterized by defective lysosomal function, leading to an accumulation of specific substrates within the lysosomes and eventual impairment of cellular function that can progress to organ failure. The liver is involved as part of a multisystemic disease in most lysosomal disorders with a wide range of presentations from asymptomatic hepatomegaly with mild abnormalities of liver enzymes to life-threatening liver dysfunction.
Chapter 32 - Lysosomal storage disorders
- from Section IV - Metabolic liver disease
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- By T. Andrew Burrow, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA, Gregory A. Grabowski, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA
- Edited by Frederick J. Suchy, University of Colorado Medical Center, Ronald J. Sokol, University of Colorado Medical Center, William F. Balistreri
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- Book:
- Liver Disease in Children
- Published online:
- 05 March 2014
- Print publication:
- 20 February 2014, pp 546-566
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Summary
Introduction
Lysosomes are membrane bound cellular organelles that contain multiple hydrolases needed for the digestion of various macromolecules including mucopolysaccharides, glycosphingolipids and oligosaccharides. The lysosomal storage diseases are a group of over 40 diseases that are characterized by defective lysosomal function, leading to an accumulation of specific substrates within the lysosomes and eventual impairment of cellular function. A schematic of the lysosomal system enzyme trafficking and substrate accumulation is shown in Figure 32.1.
These diseases are classified by the nature of the stored material that results from the defects in selected lysosomal enzymes, their cofactors, and/or enzyme or substrate transport (Table 32.1). The lysosomal storage diseases are heterogeneous, progressive, multisystem diseases that have a spectrum of ages of onset, severity, rate of progression, and organ involvement. Lysosomal storage diseases have significant morbidity and mortality in the absence of effective treatment. The majority of these diseases are autosomal recessive and, although individually rare, the combined birth prevalence is approximately 1 in 7 000 live births [2]. The diseases are traditionally diagnosed biochemically, but in many cases may also be confirmed molecularly by the identification of pathogenic mutations in one or both copies (X-linked conditions or autosomal recessive, respectively) of the specific genes.
30 - The Liver in Lysosomal Storage Diseases
- from SECTION IV - METABOLIC LIVER DISEASE
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- By T. Andrew Burrow, M.D., Resident, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio; Resident, Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, Kevin E. Bove, M.D., Professor of Pathology and Pediatrics, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio; Pediatric Pathologist, Division of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, Gregory A. Grabowski, M.D., Professor, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio; Director, Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
- Edited by Frederick J. Suchy, Mount Sinai School of Medicine, New York, Ronald J. Sokol, University of Colorado, Denver, William F. Balistreri, University of Cincinnati
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- Book:
- Liver Disease in Children
- Published online:
- 18 December 2009
- Print publication:
- 07 May 2007, pp 714-735
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Summary
Lysosomes are membrane-bound cellular organelles that contain multiple hydrolases needed for the digestion of various macromolecules, including mucopolysaccharides, glycosphingolipids, and oligosaccharides [1]. The lysosomal storage diseases are a group of more than 40 diseases that are characterized by defective lysosomal function leading to an accumulation of specific substrates within the lysosomes and eventual impairment of cellular function. A schematic of the lysosomal system, enzyme trafficking, and substrate accumulation is shown in Figure 30.1.
These diseases are classified by the nature of the stored material that results from defects in selected lysosomal enzymes, their cofactors, and/or enzyme or substrate transport (Table 30.1). The lysosomal storage diseases are heterogeneous, progressive, multisystemic diseases that have a spectrum of ages of onset, severity, rates of progression, and organ involvement. Lysosomal storage diseases have significant morbidity and mortality in the absence of effective treatment. The majority of these diseases are autosomal recessive, and although individually each is rare, the combined birth prevalence is approximately 1 in 7000 live births [2]. The diseases are traditionally diagnosed biochemically but in many cases, may also be diagnosed molecularly by the discovery of pathogenic mutations in both copies of the particular gene.
The liver is nearly always involved in lysosomal storage diseases; this can be seen at the light or electron microscopic level. The degree of clinical involvement depends on the disorder. In many cases, mild elevations in liver studies and hepatomegaly are the only manifestations. However, significant hepatic injury may be present, resulting in considerable morbidity.