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Physician's Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases pp 375–397Cite as

Peroxisomal Disorders

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Abstract

Peroxisomes contain a set of substrate-specific metabolic pathways, including the oxidation of a range of fatty acids, the biosynthesis of a special group of phospholipids (plasmalogens) and the production of bile acids. Clinically, a dysfunction of peroxisomes results in most cases in neurologic symptoms of varying extent, from severe to milder clinical forms. Ocular and hearing symptoms, dysmorphisms, liver disease and skeletal involvement are variably associated with these different disorders. Peroxisomal disorders are divided into two major categories. The first are disorders resulting from a failure to form normal peroxisomes, giving rise to multiple metabolic abnormalities. This group is named peroxisome biogenesis disorders (PBD) that can be divided into two subtypes, including (1) the Zellweger spectrum disorders and (2) rhizomelic chondrodysplasia punctata (RCDP) type 1. The second category includes the disorders, which result from the deficiency of a peroxisomal enzyme or transporter.

In single peroxisomal enzyme disorders, the basic problem is at the level of one of the enzymes or transporters involved in each of the different metabolic pathways contained in peroxisomes. Clinically, these disorders can be as severe as those in which peroxisomal biogenesis is defective. This is the case for D-bifunctional protein deficiency, peroxisomal acyl-CoA oxidase 1 deficiency and the RCDP types 2 and 3. The most common single peroxisomal enzyme disorder is the X-linked adrenoleukodystrophy (ALD)/adrenomyeloneuropathy (AMN) complex that consists of a spectrum of phenotypes varying in the age of onset and severity of clinical presentation.

The diagnosis of a peroxisomal disorder can be determined by a battery of biochemical assays in blood and/or urine and should be confirmed in cultured fibroblasts. Prenatal diagnosis is possible either by biochemical testing or by molecular analysis. Management of most peroxisomal disorders is focused on supportive care and multidisciplinary treatment of a variety of systemic complications. Specific treatment is essential in a few single enzyme disorders. Bone marrow/haematopoietic stem cell transplantation is an option for boys suffering from the cerebral form of X-ALD , at least when in the early stages.

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Acknowledgements

The authors gratefully acknowledge Mrs. Maddy Festen-Sidler and Mrs. J.A. van Leeuwen-Wesselingh for their expert preparation of the manuscript and Mr. J.P.N. Ruiter for the artwork. Supported by grants from the Dutch Organisation for Scientific Research (NWO), Medical Sciences, the European Leukodystrophy Association (Project no FP7-Health-2009-single-stage-241622), the European Union Peroxisome Project (Project no LSHG-CT-2004-512018) and the Prinses Beatrix Fonds (Project no MAR-03-216), Den Haag, the Netherlands.

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Authors and Affiliations

  1. Department of Pediatrics/Pediatric Neurology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands

    Bwee Tien Poll-The

  2. Lab Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands

    Ronald J. A. Wanders

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  1. Bwee Tien Poll-The
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Correspondence to Bwee Tien Poll-The .

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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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Poll-The, B.T., Wanders, R.J.A. (2014). Peroxisomal Disorders. 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_24

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  • DOI: https://doi.org/10.1007/978-3-642-40337-8_24

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