Printer Friendly


Cases of developmental delay or regression are among the most common and challenging in pediatrics. Phenotypic features are nonspecific and include gait disturbances, cognitive impairment, seizures, strokes, and psychiatric symptoms. Failure to detect treatable metabolic disturbances may leave patients with lifelong impairment. Newborn screening programs fail to comprehensively identify these conditions, so clinicians must be aware of the biochemical basis of these conditions and the tools available for detection.

Carbonyl groups (=C=O) are metabolized in biotin-dependent reactions. The metabolism of less-oxidized single-carbon units such as methyl (-C[H.sub.3]), methylene (-C[H.sub.2]-), and methylidine (-CH = ) groups are facilitated by folate. Folate-dependent molecular species include purines, pyrimidines, creatine, and myelin, which serve a diverse array of cellular functions from DNA synthesis to energy provision. Accumulation of homocysteine is a diagnostically sensitive but nonspecific indicator of disrupted folate metabolism. Homocysteinemia(uria) may result from nutritional deficiency, cystathionine-[beta]-synthase mutations, or errors in folate and cobalamin metabolism. There is no panacea for detecting and defining these metabolic disturbances. While targeted immunoassays for total plasma homocysteine are commonly available, metabolic investigations typically begin with comprehensive profiles of amino acids, carnitine esters, and organic acids. Homocysteine is detected in amino acid profiles as its oxidized homodimer, homocystine. Mild increases in homocysteine, therefore, may not be readily appreciated in comprehensive metabolic profiles.

Homocysteine concentrations in these disorders are similar, so adjunct metabolites must be assessed to determine the mechanism. Methionine increase is associated with cystathionine-[beta]-synthase defects, whereas a plasma methionine concentration that is within or below the reference interval suggests a folate or cobalamin-dependent mechanism. Methylmalonic acid serves as an indicator of cobalamin status because its conversion to succinate requires adenosylcobalamin. Despite the capacity to define the metabolome with increasing resolution, diagnosis and treatment approaches may still require genetic analyses. In all cases, close collaboration between the laboratory and clinician is essential to a timely diagnosis and treatment.

Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article.

Authors' Disclosures or Potential Conflicts of Interest: Upon manuscript submission, all authors completed the author disclosure form. Disclosures and/or potential conflicts of interest:

Employment or Leadership: D. Dietzen, AACC Board of Directors.

Consultant or Advisory Role: None declared.

Stock Ownership: None declared.

Honoraria: None declared.

Research Funding: None declared.

Expert Testimony: None declared.

Patents: None declared.

Dennis Dietzen *

Department of Pediatrics, Washington University School of Medicine, St. Louis, MO.

* Address correspondence to the author at: Washington University School of Medicine, Box 8116, One Childrens Place, Rm. 2N68, St. Louis, MO 63110. Fax 314-454-2274; e-mail

Received April 22, 2013; accepted April 29, 2013.

DOI: 10.1373/clinchem.2013.202762
COPYRIGHT 2013 American Association for Clinical Chemistry, Inc.
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2013 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Title Annotation:Clinical Case Study
Author:Dietzen, Dennis
Publication:Clinical Chemistry
Article Type:Report
Date:Aug 1, 2013
Previous Article:Commentary.
Next Article:Evolving role of microparticles in the pathophysiology of endothelial dysfunction.

Terms of use | Privacy policy | Copyright © 2019 Farlex, Inc. | Feedback | For webmasters