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What is it?

A multiplex DNA test which analyses a combination of genetic variants in individuals previously diagnosed with demyelinating diseases such as multiple sclerosis (MS). The results are interpreted in the context of blood biochemistry (pathology) tests, family history and lifestyle factors such as diet composition and smoking, by means of an online questionnaire. This is a novel concept called Pathology Supported Genetic Testing (PSGT).

Demyelinating diseases of the central nervous system are caused by a complex interaction between genetic, infectious and environmental factors. Research has improved our understanding of the multifactorial nature of the disease (1-5), including those involved in iron regulation, lipid metabolism, folate/vitamin B12 metabolism, haemostasis (blood flow), vitamin D metabolism, and inflammation.

Demyelinating diseases include clinically isolated syndrome (CIS), multiple sclerosis (MS), acute disseminated encephalomyelitis (ADEM), and pediatric multiple sclerosis which has several subtypes (6).

When do I recommend it?

The test was developed for patients already diagnosed with a demyelinating disease such as multiple sclerosis (MS), who would like to take control of the disease process by learning about the effects of genetic variations and their interaction with environmental risk factors. Although genes cannot be changed, their effects in causing disease may be switched on or off by certain environmental exposures. As many of the genes implicated in MS severity or disease progression are common to other chronic diseases, screening of a gene panel selected according to relevant metabolic pathways is applicable. Based on this model, MS-related genetic alterations and environmental triggers converge in a common pathogenic mechanism that compromises the production, maintenance and repair of myelin (7).

What are its benefits?

The gene variations included in the Demyelinating Diseases GeneScreen cannot be used to diagnose MS, but have been selected to provide information about how to improve quality of life by enhancing myelin repair and maintenance, when viewed in the context of lifestyle factors that can be changed by the individual. The Demyelinating Diseases GeneScreen aims to empower patients with knowledge to control and manage their disease outcome (1).

Genetic differences among patients may also affect how certain drugs and nutrients are metabolised by the body. Our approach assesses genetic and lifestyle risk factors in relation to the metabolic profile of each patient, taking into account relevant gene-drug (pharmacogenetic) and gene-diet (nutrigenetic) interactions. This test aims to improve clinical management of demyelinating diseases by means of a research-based pathology supported gene-based intervention program. This offers molecular reclassification or subtyping of patients into distinct treatment groups for individualised interventions.

A report that integrates the test results with the information on clinical indicators, family history and lifestyle will be provided. This report will also include detailed health guidelines as well as a personalised Nutrition Support Program linked to ongoing monitoring of health outcomes. The Gknowmix data integration tool enables participation of clinicians, genetic counselors, dieticians and medical scientists in the service delivery process and ongoing health outcomes research.

Scientific rationale

The body is designed to prevent and repair injuries. In the case of demyelinating diseases such as MS, oligodendrocytes (the cells that produce myelin) undergo apoptosis (cell death) through mechanisms that are only partially understood (8). The demised cells and the associated myelin are then cleared away by microglia (brain phagocytes). Simultaneously, oligodendrocyte precursor cells (adult stem cells), which are resident in the brain, mature and remyelinate the axons (1,8). Importantly, these repair mechanisms depend on the ongoing availability of raw materials (nutrients) provided in the diet and optimal biochemical pathways. Frequently genetic polymorphism of enzymes combines with a relative deficiency of substrate to impair these repair and maintenance systems. In demyelinating diseases these deficiencies can become catastrophic and produce clinical manifestations. Conversely, preemptive strategic nutrition support may add greater resilience during times of intermittent loss. A better understanding of the process of injury provides information that can ensure that both the maintenance and repair mechanisms are optimal at all times.

The Demyelinating Diseases Genescreen has been formulated to combine evidence from the scientific literature with our own experience of investigating MS cases since 1998 (9).

References

1. Van Rensburg SJ, Kotze MJ, van Toorn R. The conundrum of iron in multiple sclerosis - time for an individualised approach. Metab Brain Dis. 2012; 27: 239-253.

2. Van Rensburg SJ, Van Toorn R. The controversy of CCSVI and iron in multiple sclerosis: is ferritin the key? Neurology 2010; 75:1581-1582.

3. Van Rensburg SJ, Kotze MJ, Hon D, Haug P, Kuyler J, Hendricks M, Botha J, Potocnik FC, Matsha T, Erasmus RT. Iron and the folate-vitamin B12-methylation pathway in multiple sclerosis. Metab Brain Dis 2006;21:121-137.

4. Rooney RN, Kotze MJ, de Villiers JN, Hillermann R, Cohen JA. Multiple sclerosis, porphyria-like symptoms, and a history of iron deficiency anemia in a family of Scottish descent. Am J Med Genet 1999; 86:194-196.

5. Kotze MJ, de Villiers JN, Rooney RN, Grobbelaar JJ, Mansvelt EP, Bouwens CS, Carr J, Stander I, du Plessis L. Analysis of the NRAMP1 gene implicated in iron transport: association with multiple sclerosis and age effects. Blood Cells Mol Dis 2001;27:44-53.

6. Van Toorn R, Schoeman J, Solomons R, Rensburg M, Van Rensburg SJ. Iron status in children with recurrent episodes of tumefactive cerebral demyelination. J Child Neurol 2010; 25):1401-1407.

7. Van Rensburg SJ, Haug PD and Kotze MJ. Multiple Sclerosis. MIMS Disease Review 2009/2010, pp369-374.

8. Barnett MH, Prineas JW . Relapsing and remitting multiple sclerosis: pathology of the newly forming lesion. Ann Neurol 2004; 55:458-468.

9. Patent: 2010 01 04 - P1982ZA00. MJ Kotze, SJ van Rensburg, R Rooney, PD Haug. University of Stellenbosch and NHLS. In vitro method of diagnosis of a demyelinating disease subtype.


READ MORE ABOUT ONGOING RESEARCH: Tygerland Newsletter 2013,  pages 40-42 2013: http://www.myvirtualpaper.com/doc/stellenbosch-University/tygerland-2013-eng/2013121701/#0


THE ABOVE INFORMATION WAS COMPILED BY:

SJ van Rensburg, Associate Professor, Division of Chemical Pathology, National Health Laboratory Service and University of Stellenbosch, Tygerberg, South Africa.



To learn more please listen to a 15 min talk by Prof SJ van Rensburg at: https://www.youtube.com/watch?v=BaU6fyZRSBc


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