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Biotin-Responsive Disorders

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Inborn Metabolic Diseases

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Abstract

Two inherited defects in biotin metabolism are known: holocarboxylase synthetase (HCS) deficiency and biotinidase deficiency. Both lead to deficiency of all biotindependent carboxylases, i.e. to multiple carboxylase deficiency (MCD). In HCS deficiency, the binding of biotin to apocarboxylases is impaired. In biotinidase deficiency, biotin depletion ensues from the inability to recycle endogenous biotin and to utilize protein-bound biotin from the diet. As the carboxylases play an essential role in the catabolism of several amino acids, in gluconeogenesis and in fatty-acid synthesis, their deficiency provokes multiple, life-threatening metabolic derangements, eliciting characteristic organic aciduria and neurological symptoms. The clinical presentation is extremely variable in both disorders. Characteristic symptoms include metabolic acidosis, hypotonia, seizures, ataxia, impaired consciousness and cutaneous symptoms, such as skin rash and alopecia. All patients with biotinidase and a majority of patients with HCS deficiency respond dramatically to oral therapy with pharmacological doses of biotin. Delayed diagnosis and treatment in biotinidase deficiency may result in irreversible neurological damage. A few patients with HCS deficiency show a partial or even no response to biotin and seem to have an impaired long-term outcome. Acquired biotin deficiency, which also causes MCD, is extremely rare. A defect in biotin transport has been reported in a single child; however the genetic defect remains unresolved to date. Biotin-Responsive Basal Ganglia Disease (BRBGD) is a recently described subacute encephalopathy which disappears within a few days without neurological sequelae if biotin is administered early.

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Author information

Authors and Affiliations

  1. Division of Metabolism and Molecular Pediatrics, University Children’s Hospital, Steinwiesstr. 75, 8032, Zurich, Switzerland

    Matthias R. Baumgartner

  2. Metabolic Unit, University Children’s Hospital, Romergasse 8, 4005, Basel, Switzerland

    Terttu Suormala

Authors
  1. Matthias R. Baumgartner
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  2. Terttu Suormala
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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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Baumgartner, M.R., Suormala, T. (2006). Biotin-Responsive Disorders. 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_27

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  • DOI: https://doi.org/10.1007/978-3-540-28785-8_27

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