Enzymatic diagnosis of homocystinuria by determination of cystathionine-ß-synthase activity in plasma using LC-MS/MS
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
25218699
DOI
10.1016/j.cca.2014.09.009
PII: S0009-8981(14)00405-7
Knihovny.cz E-resources
- Keywords
- Cystathionine ß-synthase activity, Homocystinuria, LC-MS/MS, Pyridoxine response,
- MeSH
- Chromatography, Liquid MeSH
- Cystathionine beta-Synthase blood genetics MeSH
- Cystathionine blood MeSH
- Child MeSH
- Adult MeSH
- Gene Expression MeSH
- Genotype MeSH
- Homocystinuria blood diagnosis genetics MeSH
- Homozygote MeSH
- Infant MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Mutation * MeSH
- Child, Preschool MeSH
- Pedigree MeSH
- Aged MeSH
- Tandem Mass Spectrometry MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Infant MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Child, Preschool MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Cystathionine beta-Synthase MeSH
- Cystathionine MeSH
BACKGROUND: Cystathionine β-synthase (CBS) is released into plasma from organs expressing this enzyme. Decreased plasma CBS activity has been demonstrated in CBS-deficient patients with 16 different genotypes. The aim of this study was to determine plasma CBS activity in patients carrying 11 additional genotypes using two LC-MS/MS methods. Patients and methods CBS activity was measured in EDTA or heparin plasma using either a previously described or a newly developed LC-MS/MS method optimized for analysis of the reaction product, 3,3-(2)H2-cystathionine, as its butyl ester derivative. We analyzed plasma samples from 26 CBS-deficient patients with known genotypes and 57 controls. RESULTS: We developed a new LC-MS/MS method for simple and sensitive determination of CBS activity. Plasma CBS activity was low (i.e., 0.001-0.036 of the multiples of median control values, MoM) in patients homozygous for the prevalent Hispanic mutation c.572C>T (p.T191M) but was highly elevated (2.95 MoM) in a single patient homozygous for the c.1330G>A (p.D444N) mutation. Patients with the remaining nine genotypes exhibited decreased activities (0.00-0.22 MoM), which did not overlap with the controls (0.29-2.10 MoM). CONCLUSIONS: The determination of CBS activity in plasma is a rapid and non-invasive procedure for detecting a subgroup of CBS-deficient patients with distinct genotypes.
References provided by Crossref.org
Recent therapeutic approaches to cystathionine beta-synthase-deficient homocystinuria
A proactive genotype-to-patient-phenotype map for cystathionine beta-synthase
Guidelines for the diagnosis and management of cystathionine beta-synthase deficiency
