Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-76fb5796d-dfsvx Total loading time: 0 Render date: 2024-04-25T07:59:33.018Z Has data issue: false hasContentIssue false

Chapter 32 - Lysosomal Storage Disorders in Children

from Section IV - Metabolic Liver Disease

Published online by Cambridge University Press:  19 January 2021

By
Pramod K. Mistry ,
Beth L. Thurberg  and
Gregory A. Grabowski
Edited by
Frederick J. Suchy ,
Ronald J. Sokol  and
William F. Balistreri
Edited in association with
Jorge A. Bezerra ,
Cara L. Mack  and
Benjamin L. Shneider
Frederick J. Suchy
Affiliation:
University of Colorado, Children’s Hospital Colorado, Aurora
Ronald J. Sokol
Affiliation:
University of Colorado, Children’s Hospital Colorado, Aurora
William F. Balistreri
Affiliation:
Cincinnati Children’s Hospital Medical Center, Cincinnati
Jorge A. Bezerra
Affiliation:
Cincinnati Children’s Hospital Medical Center, Cincinnati
Cara L. Mack
Affiliation:
University of Colorado, Children’s Hospital Colorado, Aurora
Benjamin L. Shneider
Affiliation:
Texas Children’s Hospital, Houston
Get access

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.

Type
Chapter
Information
Liver Disease in Children , pp. 570 - 592
Publisher: Cambridge University Press
Print publication year: 2021

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Muenzer, J, Fisher, A. Advances in the treatment of mucopolysaccharidosis type I. N Engl J Med 2004;350:1932–4.CrossRefGoogle ScholarPubMed
Poorthuis, BJ, Wevers, RA, Kleijer, WJ, et al. The frequency of lysosomal storage diseases in the Netherlands. Hum Genet 1999;105(1–2):151–6.Google Scholar
Grabowski, GA, Petsko, GA, Kolodny, EH. Gaucher disease. In Valle, D, Beaudet, AL, Vogelstein, B, et al. (Eds.), The Online Metabolic & Molecular Bases of Inherited Disease. Available at: www.ommbid.com [last accessed June 24, 2020].Google Scholar
James, SP, Stromeyer, FW, Chang, C, Barranger, JA. Liver abnormalities in patients with Gaucher’s disease. Gastroenterology 1981;80:126–33.CrossRefGoogle ScholarPubMed
Barbier, C, Devisme, L, Dobbelaere, D, et al. Neonatal cholestasis and infantile Gaucher disease: a case report. Acta Paediatr 2002;91:1399–401.Google Scholar
Weinreb, NJ, Charrow, J, Andersson, HC, et al. Effectiveness of enzyme replacement therapy in 1028 patients with type 1 Gaucher disease after 2 to 5 years of treatment: a report from the Gaucher Registry. Am J Med 2002;113:112–19.Google Scholar
Lukina, E, Watman, N, Arreguin, EA, et al. Improvement in hematological, visceral, and skeletal manifestations of Gaucher disease type 1 with oral eliglustat tartrate (Genz-112638) treatment: 2-year results of a phase 2 study. Blood 2010;116:4095–8.Google Scholar
Mistry, PK, Lukina, E, Ben Turkia, H, et al. Effect of oral eliglustat on splenomegaly in patients with Gaucher disease type 1: the ENGAGE randomized clinical trial. JAMA 2015;313(7):695–706. doi:10.1001/jama.2015.459CrossRefGoogle ScholarPubMed
Meikle, PJ, Hopwood, JJ, Clague, AE, Carey, WF. Prevalence of lysosomal storage disorders. JAMA 1999;281:249–54.CrossRefGoogle ScholarPubMed
Schuchman, EH, Desnick, RJ. Niemann–Pick disease types A and B: acid sphingomyelinase deficiencies. In Valle, D, Beaudet, AL, Vogelstein, B, et al. (Eds.), The Online Metabolic & Molecular Bases of Inherited Disease. Available at: www.ommbid.com [last accessed June 24, 2020].Google Scholar
Wasserstein, MP, Desnick, RJ, Schuchman, EH, et al. The natural history of type B Niemann–Pick disease: results from a 10-year longitudinal study. Pediatrics 2004;114: e672–e677.CrossRefGoogle ScholarPubMed
Takahashi, T, Akiyama, K, Tomihara, M, et al. Heterogeneity of liver disorder in type B Niemann–Pick disease. Hum Pathol 1997;28:385–8.Google Scholar
Thurberg, BL, Wasserstein, MP, Schiano, T, O’Brien, F, Richards, S, Cox, GF, McGovern, MM. Liver and skin histopathology in adults with acid sphingomyelinase deficiency (Niemann-Pick disease type B). Am J Surg Pathol 2012;36(8):1234–46.CrossRefGoogle ScholarPubMed
Thurberg, BL, Wasserstein, MP, Jones, S, Schiano, T, Cox, GF, Puga, AC. Clearance of hepatic sphingomyelin by olipudase alfa is associated with improvement in lipid profiles in acid sphingomyelinase deficiency. Am J Surg Pathol 2016;40(9):1232–42.CrossRefGoogle ScholarPubMed
Wasserstein, MP, Jones, SA, Soran, H, Diaz, G, Lippa, N, Thurberg, BL, Culm-Merdek, K, Shamiyeh, E, Inguilizian, H, Cox, GF, Puga, AC. Successful within-patient dose escalation of olipudase alfa in acid sphingomyelinase deficiency. Mol Genet Metab 2015;116(1–2):88–97.CrossRefGoogle ScholarPubMed
McGovern, MM, Wasserstein, MP, Kirmse, B, Duvall, WL, Schiano, T, Thurberg, BL, Richards, S, Cox, GF. Novel first-dose adverse drug reactions during a Phase 1 trial of recombinant human acid sphingomyelinase (rhASM) in adults with Niemann-Pick disease type B (acid sphingomyelinase deficiency). Genet Med 2016;18(1):34–40.Google Scholar
Victor, S, Coulter, JB, Besley, GT, et al. Niemann–Pick disease: sixteen-year follow-up of allogeneic bone marrow transplantation in a type B variant. J Inherit Metab Dis 2003;26:775–85.CrossRefGoogle Scholar
Levade, T, Sandhoff, K, Schulze, H, Medin, JA. Acid ceramidase deficiency: Farber lipogranulomatosis. In Valle, D, Beaudet, AL, Vogelstein, B, et al. (Eds.), The Online Metabolic & Molecular Bases of Inherited Disease. Available at: www.ommbid.com [last accessed June 24, 2020].Google Scholar
Kattner, E, Schafer, A, Harzer, K. Hydrops fetalis: manifestation in lysosomal storage diseases including Farber disease. Eur J Pediatr 1997;156:292–5.CrossRefGoogle ScholarPubMed
Yeager, AM, Uhas, KA, Coles, CD, et al. Bone marrow transplantation for infantile ceramidase deficiency (Farber disease). Bone Marrow Transplant 2000;26:357–63.CrossRefGoogle ScholarPubMed
Vormoor, J, Ehlert, K, Groll, AH, et al. Successful hematopoietic stem cell transplantation in Farber disease. J Pediatr 2004;144:132–4.CrossRefGoogle ScholarPubMed
Suzuki, Y, Nanba, E, Matsuda, J, Higaki, K, Oshima, A. B-Galactosidase deficiency (B-galactosidosis): GM1 gangliosidosis and morquio B disease. In Valle, D, Beaudet, AL, Vogelstein, B, et al. (Eds.), The Online Metabolic & Molecular Bases of Inherited Disease. Available at: www.ommbid.com [last accessed June 24, 2020].Google Scholar
Vanier, MT, Millat, G. Niemann–Pick disease type C. Clin Genet 2003;64:269–81.Google Scholar
Vanier, MT. Niemann–Pick disease type C. Orphanet J Rare Dis 2010;5:16.Google Scholar
Patterson, MC, Vanier, MT, Suzuki, K, et al. Niemann–Pick disease type C: a lipid trafficking disorder. In Valle, D, Beaudet, AL, Vogelstein, B, et al. (Eds.), The Online Metabolic & Molecular Bases of Inherited Disease. Available at: www.ommbid.com [last accessed June 24, 2020].Google Scholar
Patterson, M. (1993). Niemann–Pick disease type C. In Pagon, RA, Bird, TD, Dolan, CR, Stephens, K (Eds.), GeneReviews. Seattle, WA: University of Washington.Google Scholar
Kelly, DA, Portmann, B, Mowat, AP, Sherlock, S, Lake, BD. Niemann–Pick disease type C: diagnosis and outcome in children, with particular reference to liver disease. J Pediatr 1993;123:242–7.CrossRefGoogle ScholarPubMed
Gilbert, EF, Callahan, J, Viseskul, C, Opitz, JM. Niemann–Pick disease type C. Pathological, histochemical, ultrastructural and biochemical studies. Eur J Pediatr 1981;136:263–74.CrossRefGoogle ScholarPubMed
Yerushalmi, B, Sokol, RJ, Narkewicz, MR, et al. Niemann–Pick disease type C in neonatal cholestasis at a North American Center. J Pediatr Gastroenterol Nutr 2002;35:44–50.CrossRefGoogle Scholar
Zervas, M, Somers, KL, Thrall, MA, Walkley, SU. Critical role for glycosphingolipids in Niemann–Pick disease type C. Curr Biol 2001;11:1283–7.CrossRefGoogle ScholarPubMed
Wraith, JE, Vecchio, D, Jacklin, E, et al. Miglustat in adult and juvenile patients with Niemann–Pick disease type C: long-term data from a clinical trial. Mol Genet Metab 2010;99:351–7.Google Scholar
Ashe, KM, Bangari, D, Li, L, et al. Iminosugar-based inhibitors of glucosylceramide synthase increase brain glycosphingolipids and survival in a mouse model of Sandhoff disease. PLOS One 2011;6:e21758.CrossRefGoogle Scholar
Thomas, GH. Disorders of glycoprotein degradation: α-mannosidosis, B- mannosidosis, fucosidosis, and sialidosis. In Valle, D, Beaudet, AL, Vogelstein, B, et al. (Eds.), The Online Metabolic & Molecular Bases of Inherited Disease. Available at: www.ommbid.com [last accessed June 24, 2020].Google Scholar
Willems, PJ, Gatti, R, Darby, JK, et al. Fucosidosis revisited: a review of 77 patients. Am J Med Genet 1991;38:111–31.Google Scholar
Freitag, F, Blumcke, S, Spranger, J. Hepatic ultrastructure in mucolipidosis I (lipomucopolysaccharidosis). Virchows Arch B Cell Pathol 1971;7:189–204.Google Scholar
Vellodi, A, Cragg, H, Winchester, B, et al. Allogeneic bone marrow transplantation for fucosidosis. Bone Marrow Transplant 1995;15:153–8.Google Scholar
Monus, Z, Konyar, E, Szabo, L. Histomorphologic and histochemical investigations in mannosidosis. A light and electron microscopic study. Virchows Arch B Cell Pathol 1977;26:159–73.Google Scholar
d’Azzo, A, Andria, G, Strisciuglio, P, Galjaard, H. Galactosialidosis. In Valle, D, Beaudet, AL, Vogelstein, B, et al. (Eds.), The Online Metabolic & Molecular Bases of Inherited Disease. Available at: www.ommbid.com [last accessed June 24, 2020].Google Scholar
van der Spoel, A, Bonten, E, d’Azzo, A. Transport of human lysosomal neuraminidase to mature lysosomes requires protective protein/cathepsin A. EMBO J 1998;17:1588–97.Google Scholar
Hirschhorn, R, Reuser, AJJ. Glycogen storage disease type II: acid α- glucosidase (acid maltase) deficiency. In Valle, D, Beaudet, AL, Vogelstein, B, et al. (Eds.), The Online Metabolic & Molecular Bases of Inherited Disease. Available at: www.ommbid.com [last accessed June 24, 2020].Google Scholar
van den Hout, HM, Hop, W, van Diggelen, OP, et al. The natural course of infantile Pompe’s disease: 20 original cases compared with 133 cases from the literature. Pediatrics 2003;112:332–40.Google Scholar
Leslie, N, Tinkle, B. (1993). Glycogen storage disease type II (Pompe disease). In Pagon, RA, Bird, TD, Dolan, CR, Stephens, K (Eds.), GeneReviews. Seattle, WA: University of Washington.Google Scholar
Kishnani, PS, Howell, RR. Pompe disease in infants and children. J Pediatr 2004;144(5 Suppl.):S35–43.Google Scholar
Hagemans, ML, Winkel, LP, Van Doorn, PA, et al. Clinical manifestation and natural course of late-onset Pompe’s disease in 54 Dutch patients. Brain 2005;128(Pt 3):671–7.Google Scholar
Kishnani, PS, Corzo, D, Leslie, ND, et al. Early treatment with alglucosidase alpha prolongs long-term survival of infants with Pompe disease. Pediatr Res 2009;66:329–35.Google Scholar
Assmann, G, Seedorf, U. Acid lipase deficiency: Wolman disease and cholesteryl ester storage disease. In Valle, D, Beaudet, AL, Vogelstein, B, et al. (Eds.), The Online Metabolic & Molecular Bases of Inherited Disease. Available at: www.ommbid.com [last accessed June 24, 2020].Google Scholar
Muntoni, S, Wiebusch, H, Jansen-Rust, M, et al. Prevalence of cholesteryl ester storage disease. Arterioscler Thromb Vasc Biol 2007;27:1866–8.Google Scholar
Grabowski, G, Bove, K, Du, H. (2004). Lysosomal acid lipase deficiencies: Wolman disease and cholesteryl ester storage disease. In Walker, WA, Goulet, OJ, Kleinman, RE (Eds.), Pediatric Gastrointestinal Disease: Pathophysiology, Diagnosis and Management (pp. 1429–39). Hamilton, ON: Decker.Google Scholar
Krivit, W, Freese, D, Chan, KW, Kulkarni, R. Wolman’s disease: a review of treatment with bone marrow transplantation and considerations for the future. Bone Marrow Transplant 1992;10(Suppl. 1):97–101.Google ScholarPubMed
Valle, D, Beaudet, AL, Vogelstein, B, et al. (Eds.). In Valle, D, Beaudet, AL, Vogelstein, B, et al. (Eds.), The Online Metabolic & Molecular Bases of Inherited Disease. Available at: www.ommbid.com [last accessed June 24, 2020].Google Scholar
Parfrey, NA, Hutchins, GM. Hepatic fibrosis in the mucopolysaccharidoses. Am J Med 1986;81:825–9.CrossRefGoogle ScholarPubMed
Kornfeld, S, Sly, WS. I-cell disease and pseudo-Hurler polydystrophy: disorders of lysosomal enzyme phosphorylation and localization. In Valle, D, Beaudet, AL, Vogelstein, B, et al. (Eds.), The Online Metabolic & Molecular Bases of Inherited Disease. Available at: www.ommbid.com [last accessed June 24, 2020].Google Scholar
Pinto, R, Caseiro, C, Lemos, M, et al. Prevalence of lysosomal storage diseases in Portugal. Eur J Hum Genet 2004;12:87–92.CrossRefGoogle ScholarPubMed
Kelly, TE, Thomas, GH, Taylor, HA Jr., et al. Mucolipidosis III (pseudo-Hurler polydystrophy): clinical and laboratory studies in a series of 12 patients. Johns Hopkins Med J 1975;137:156–75.Google Scholar
Cathey, SS, Leroy, JG, Wood, T, et al. Phenotype and genotype in mucolipidoses II and III alpha/beta: a study of 61 probands. J Med Genet 2010;47:38–48.Google Scholar
Kenyon, KR, Sensenbrenner, JA, Wyllie, RG. Hepatic ultrastructure and histochemistry in mucolipidosis II (I-cell disease). Pediatr Res 1973;7:560–8.Google Scholar
Hopwood, JJ, Ballabio, A. Multiple sulfatase deficiency and the nature of the sulfatase family. In Valle, D, Beaudet, AL, Vogelstein, B, et al. (Eds.), The Online Metabolic & Molecular Bases of Inherited Disease. Available at: www.ommbid.com [last accessed June 24, 2020].Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×