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Lysosomal Storage Disorders Including Neuronal Ceroid Lipofuscinoses

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Physician's Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases

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Abstract

Metabolic disorders that affect the lysosomal degradation of complex carbohydrates, lipids, and proteins are associated with a wide variety of clinical symptoms. At the severe end of the clinical spectrum, neurological symptoms are common and go along with significant brain pathology. The high abundance of sphingolipids in brain partially explains the major neurodegenerative effect of disturbed sphingolipid breakdown. In fact, sphingolipidoses frequently present with an involvement of the cerebral white matter. Other lysosomal disorders, in particular the neuronal ceroid lipofuscinoses (NCLs), primarily affect the cerebral grey matter. The NCLs share the lysosomal accumulation of autofluorescent storage material (lipofuscin) and often result from the disturbed degradation of hydrophobic proteins. The below table lists lysosomal storage diseases that are associated with neurodegeneration. At the milder end of the clinical spectrum, variable degrees of organ involvement exist, such as renal and cardiac disease in Fabry disease and hepatosplenomegaly with bone symtoms in gaucher disease. Neurological involvement is less prominent in these phenotypes.

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Authors and Affiliations

  1. Division of Endocrinology and Metabolism, Department of Internal Medicine, F5-170, Academic Medical Center, University of Amsterdam, 22700, 1100 DE, Amsterdam, The Netherlands

    Carla Hollak

  2. Department of Pediatrics, University Medical Center Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Germany

    Matthias Kettwig & Lars Schlotawa

  3. Department of Pediatrics, University of Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Germany

    Robert Steinfeld

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  1. Carla Hollak
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  2. Matthias Kettwig
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  3. Lars Schlotawa
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  4. Robert Steinfeld
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Correspondence to Robert Steinfeld .

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Editors and Affiliations

  1. Department of General Pediatrics, University Children's Hospital, Division of Inborn Metabolic Diseases, Heidelberg, Germany

    Nenad Blau

  2. Laboratory Genetic Metabolic Diseases, University of Amsterdam Academic Medical Centre, Amsterdam, The Netherlands

    Marinus Duran

  3. Section of Clinical Pharmacology, Washington State University, Spokane, Washington, USA

    K Michael Gibson

  4. Division of Metabolism, Department of Pediatric Medicine, Bambino Gesù Children’s Research Hospital, Rome, Italy

    Carlo Dionisi Vici

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Hollak, C., Kettwig, M., Schlotawa, L., Steinfeld, R. (2014). Lysosomal Storage Disorders Including Neuronal Ceroid Lipofuscinoses. In: Blau, N., Duran, M., Gibson, K., Dionisi Vici, C. (eds) Physician's Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-40337-8_25

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