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Disorders of Cholesterol Synthesis

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Inborn Metabolic Diseases

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Abstract

Eight distinct inherited disorders have been linked to specific enzyme defects in the isoprenoid/cholesterol biosynthetic pathway after the finding of abnormally increased levels of intermediate metabolites in tissues and/or body fluids of patients followed by the demonstration of disease-causing mutations in genes encoding the implicated enzymes. Two of these disorders are due to a defect of the enzyme mevalonate kinase and affect the synthesis of all isoprenoids. Patients with these disorders characteristically present with recurrent episodes of high fever associated with abdominal pain, vomiting and diarrhoea, (cervical) lymphadenopathy, hepatosplenomegaly, arthralgia and skin rash, and may present with additional congenital anomalies.

The remaining six enzyme defects specifically affect the synthesis of cholesterol and involve four autosomal recessive and two X-linked dominant inherited syndromes. Patients afflicted with one of these defects present with multiple congenital and morphogenic anomalies, including internal organ, skeletal and/or skin abnormalities, and/or a marked delay in psychomotor development reflecting cholesterol’s pivotal role in human embryogenesis and development.

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Authors and Affiliations

  1. Laboratory for Genetic Metabolic Diseases (F0-224), Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands

    Hans R. Waterham

  2. Biochemistry Unit, Institute of Child Health, Great Ormond Street Hospital for Children, 30 Guilford Street, London, WC1N 1EH, UK

    Peter T. Clayton

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  1. Hans R. Waterham
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  2. Peter T. Clayton
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Editor information

Editors and Affiliations

  1. Department of Pediatrics, University Hospital Groningen, Burgemeester Weertslaan 31, 8162 DP, Epe, The Netherlands

    John Fernandes

  2. Unité de Métabolisme, Département de Pédiatrie, Hôpital Necker Enfants Malades, 149 Rue de Sèvres, 75043, Paris Cedex 15, France

    Jean-Marie Saudubray

  3. Metabolic Research Group, Christian de Duve Institute of Cellular Pathology, University of Louvain Medical School, Avenue Hippocrate 75-39, 1200, Brussels, Belgium

    Georges van den Berghe

  4. Willink Biochemical Genetics Unit, Royal Manchester Children’s Hospital, Hospital Road, Pendlebury, Manchester, M27 4HA, UK

    John H. Walter

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© 2006 Springer Medizin Verlag Heidelberg

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Waterham, H.R., Clayton, P.T. (2006). Disorders of Cholesterol Synthesis. In: Fernandes, J., Saudubray, JM., van den Berghe, G., Walter, J.H. (eds) Inborn Metabolic Diseases. Springer, Berlin, Heidelberg . https://doi.org/10.1007/978-3-540-28785-8_33

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  • DOI: https://doi.org/10.1007/978-3-540-28785-8_33

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-28783-4

  • Online ISBN: 978-3-540-28785-8

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