<abstract xmlns="http://www.w3.org/1999/xhtml">

<p>This review presents clinical patterns that should trigger homocysteine measurement in blood, as well as the further diagnostic work-up focused on inborn errors of metabolism and disorders of vitamin B12 (cobalamin) absorption and supply. The numerous conditions (e.g. cardiovascular disease, Alzheimer’s disease) for which mild-to-moderate hyperhomocysteinaemia caused by genetic polymorphisms or acquired reasons is considered a risk factor are beyond the scope of this review.</p>
<p>Homocysteine is a sulphur-containing amino acid, which is derived from the amino acid methionine. Homocysteine is either trans-sulphurated to form cystathionine and then cysteine, or re-methylated to methionine. The trans-sulphuration reaction depends on the enzyme cystathionine beta synthase and its cofactor vitamin B6. The re-methylation reaction not only involves the enzymes methionine synthase and methionine synthase reductase but also depends on the cofactor cobalamin and on the provision of methyl groups from the folate cycle. Because the homocysteine–methionine cycle provides for the vast majority of methyl groups in the body, it is central to numerous pathways that depend on methyl group supply, such as creatine synthesis or DNA methylation. Based on this premise, the severity of clinical presentations of inborn errors of metabolism, such as classical homocystinuria or the cobalamin C (cblC) defect, affecting this pathway is unsurprising.</p></abstract>

This review presents clinical patterns that should trigger homocysteine measurement in blood, as well as the further diagnostic work-up focused on inborn errors of metabolism and disorders of vitamin B12 (cobalamin) absorption and supply. The numerous conditions (e.g. cardiovascular disease, Alzheimer’s disease) for which mild-to-moderate hyperhomocysteinaemia caused by genetic polymorphisms or acquired reasons is considered a risk factor are beyond the scope of this review.
Homocysteine is a sulphur-containing amino acid, which is derived from the amino acid methionine. Homocysteine is either trans-sulphurated to form cystathionine and then cysteine, or re-methylated to methionine. The trans-sulphuration reaction depends on the enzyme cystathionine beta synthase and its cofactor vitamin B6. The re-methylation reaction not only involves the enzymes methionine synthase and methionine synthase reductase but also depends on the cofactor cobalamin and on the provision of methyl groups from the folate cycle. Because the homocysteine–methionine cycle provides for the vast majority of methyl groups in the body, it is central to numerous pathways that depend on methyl group supply, such as creatine synthesis or DNA methylation. Based on this premise, the severity of clinical presentations of inborn errors of metabolism, such as classical homocystinuria or the cobalamin C (cblC) defect, affecting this pathway is unsurprising.

When to measure plasma homocysteine and how to place it in context: The homocystinurias

Journal of Mother and Child

This work is licensed under the Creative Commons Attribution 4.0 International License.

This review presents clinical patterns that should trigger homocysteine measurement in blood, as well as the further diagnostic work-up focused on inborn...

When to measure plasma homocysteine and how to place it in context: The homocystinurias

Article Category: Review paper

Published Online: Oct 02, 2020

Page range: 39 - 46

DOI: https://doi.org/10.34763/jmotherandchild.20202402si.2016.000007

Keywords
re-methylation, cystathionine beta synthase deficiency, MTHFR deficiency, vitamin B12, cobalamin, gastric intrinsic factor, Imerslund-Graesbeck syndrome, transcobalamin, TCN2

© 2020 Martina Huemer, published by Sciendo

This work is licensed under the Creative Commons Attribution 4.0 International License.

When to measure plasma homocysteine and how to place it in context: The homocystinurias

Article Category: Review paper

Published Online: Oct 02, 2020

Page range: 39 - 46

DOI: https://doi.org/10.34763/jmotherandchild.20202402si.2016.000007

Keywordsre-methylation, cystathionine beta synthase deficiency, MTHFR deficiency, vitamin B12, cobalamin, gastric intrinsic factor, Imerslund-Graesbeck syndrome, transcobalamin, TCN2

© 2020 Martina Huemer, published by Sciendo

This work is licensed under the Creative Commons Attribution 4.0 International License.

Keywords
re-methylation, cystathionine beta synthase deficiency, MTHFR deficiency, vitamin B12, cobalamin, gastric intrinsic factor, Imerslund-Graesbeck syndrome, transcobalamin, TCN2