101. Enzyme Defects and the Skeleton

  1. Clifford J. Rosen MD
  1. Michael P. Whyte

Published Online: 19 JUL 2013

DOI: 10.1002/9781118453926.ch101

Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, Eighth Edition

Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, Eighth Edition

How to Cite

Whyte, M. P. (2013) Enzyme Defects and the Skeleton, in Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, Eighth Edition (ed C. J. Rosen), John Wiley & Sons, Inc., Ames, USA. doi: 10.1002/9781118453926.ch101

Publication History

  1. Published Online: 19 JUL 2013

ISBN Information

Print ISBN: 9781118453889

Online ISBN: 9781118453926

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Keywords:

  • alkaptonuria;
  • copper transport;
  • enzyme defects;
  • homocystinuria;
  • hypophosphatasia (HPP);
  • mucopolysaccharidoses;
  • skeletal disease

Summary

Inborn errors of metabolism from enzyme deficiencies can importantly affect the skeleton. This chapter reviews the five types of enzyme defects, which include hypophosphatasia (HPP), mucopolysaccharidoses, homocystinuria, alkaptonuria, and disorders of copper transport. Approximately 350 cases of HPP have been reported, showing a remarkable range of severity with four overlapping clinical forms described according to patient age when skeletal disease is discovered: perinatal, infantile, childhood, and adult. Mucopolysaccharidoses are increasingly treated by marrow cell transplantation or enzyme-replacement therapy. Alkaptonuria is a rare autosomal recessive disorder caused by a deficiency of homogentisic acid oxidase from loss-of-function mutations within the AKU gene. In Menkes disease, inherited as an X-linked recessive trait, boys develop Cu2+ deficiency that leads to kinky, sparse hair, and central nervous system (CNS) disease including mental retardation, seizures, and intracranial hemorrhage.