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Demonstration of the diagnostic utility of a novel and fast method for plasma total homocysteine in representative target populations

Objective

Objectives:
1. To evaluate the performance (capacity, robustness, precision etc.) of the novel tHcy assay in 4 different laboratories, located in 4 European countries, in comparison with HPLC tHcy determinations.
2. To apply the two assay variants for the measurement of tHcy in three large populations reflecting future clinical practice, under different conditions and complementary requirements for this diagnostic test. The populations and assay parameters that will be evaluated are as follows:


Population
Sample size
Sample volume
Assay throughput
Accuracy and precision
To be assessed
elderly
4000
50-100 I1L
high
intermediate
Prevalence of elevated tHcy
Vit. status/cogn. Impairment
Vascular-risk patients
7000
50-100 pL
high
High, CV<5%
Cardiovascular risk;
Vitamin response
newborn
65000
<25 I1L
Very high
Low, CV<15%5Lhyperhomocysteinemia
3. To validate and confirm the diagnostic utility of tHcy when used in conjunction with complementary assays in selected samples. The complementary tests will include plasma and red cell folate, plasma cobalamin, cobalamin binding proteins, vitamin B6, methylmalonic acid and genetic analyses.
4. To establish guidelines for tHcy determination in different patient categories, with particular emphasis on the diagnosis of vitamin deficiencies, vascular risk and inborn errors in the new-born.
5. To disseminate information to the relevant target personnel on the performance, specification, and application of the novel tHcy assays in comparison with current complementary diagnostic assays.

Plasma total homocysteine (tHcy) is an established marker of several common diseases. It is a strong an independent risk factor for cardiovascular diseases (WHO Techn. Rep. Series (1994) 841), a sensitive marker of cobalamin (B 12) and folate deficiencies, and is related to birth defects in pregnant women and to cognitive impairment in the elderly. The clinicians have recently recognised the diagnostic utility of tHcy determinations. In Scandinavia, physicians now request almost 5000 tHcy analyses/million persons per year. The current assays which are based on HPLC and GC-MS techniques, are time consuming, expensive and require a highly skilled technical staff, which limits their application in most routine clinical chemistry laboratories.

Axis Biochemicals has developed and patented two variants of a tHcy immunoassay; one homogenous assay is adapted to the IMx system (FPLA) and the other is an enzyme immunoassay (EIA). Both variants are suitable for small clinical chemistry laboratories, and should be widely available and relative inexpensive compared with existing methods. The goal of this project is to determine the diagnostic utility of these novel assays, to evaluate any problems associated with their use, and to demonstrate the technical and socioeconomic advantages when assessed under realistic operating conditions in a range of clinical settings.

The objectives of the present proposal are:
1. To evaluate the performance (capacity, robustness, precision etc.) of the novel tHcy assay in 4 different laboratories, located in 4 European countries, in comparison with HPLC tHcy determinations;
2. To apply the two assay variants for the measurement of tHcy in three large populations reflecting future clinical practice, under different conditions and complementary requirements for this diagnostic test.
The populations and assay parameters which will be evaluated are as follows: Assay requirements: Population Sample size Sample Assay Accuracy To be volume throughput and precision assessed. Elderly 4000 50-100;- high intermediate Prevalenc of elevated tHcyl Vit. status /cogn. Impairment.
Vascular risk 7000 50-100;- high high Cardiovascul patients CV<5% risk. Vitamin response. Newborn 65000 <25;- very high low homocystinur CV<15% Hyperhomo- cysteinemia;
3. To validate and confirm the diagnostic utility of tHcy when used in conjunction with complementary assays in selected samples. The complementary tests will include plasma and red cell folate, plasma cobalamin, cobalamin binding proteins, vitamin B6, methylmalonic acid and genetic analyses;
4. To establish guidelines for tHcy determination in different patient categories, with particular emphasis on the diagnosis of vitamin deficiencies, vascular risk and inborn errors in the newborn;
5. To disseminate information to the relevant target personnel on the performance, specification, and application of the novel tHcy assays in comparison with current complementary diagnostic assays.

KEYWORDS: clinical chemistry, immunoassay, homocysteine, vitamin B12, folate, vitamin deficiency, vascular disease, inborn errors of metabolism, elderly, cognitive function.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

Universitetet i Bergen
Address
Armauer Hansens Hus
5021 Bergen
Norway

Participants (4)

AXIS Biochemicals ASA
Norway
Address
30,Helgesensgt.
0515 Oslo
THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
United Kingdom
Address
Mansfield Road
Oxford
THE PROVOST, FELLOWS AND SCHOLARS OF THE COLLEGE OF THE HOLY AND UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN HEREINAFTER TRINITY COLLEGE DUBLIN
Ireland
Address
College Green
4 Dublin
UNIVERSITY OF AARHUS
Denmark
Address
44,Brendstrupgaardsvej
8200 Aarhus C