Pathology-supported genetic testing as a method for disability prevention in multiple sclerosis (MS). Part II. Insights from two MS cases

Susan J van Rensburg¹, Coenraad Hattingh², Clint Johannes³, Kelebogile E Moremi⁴, Armand V Peeters², Carel J van Heerden⁵, Rajiv T Erasmus², Annalise E Zemlin⁴, Merlisa C Kemp⁶, Mariaan Jaftha⁶, Aye Aye Khine⁴, Felix C V Potocnik⁷, Lindiwe Whati⁸, Penelope Engel-Hills⁹, Ronald van Toorn¹⁰, Maritha J Kotze⁴

Affiliations

¹ Division of Chemical Pathology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa. sjvr@sun.ac.za.
² Division of Chemical Pathology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
³ Department of Internal Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg Academic Hospital, Cape Town, South Africa.
⁴ Division of Chemical Pathology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, National Health Laboratory Service (NHLS), Cape Town, South Africa.
⁵ Central Analytical Facility (CAF), DNA Sequencing Unit, Stellenbosch University, Stellenbosch, South Africa.
⁶ Department of Medical Imaging and Therapeutic Sciences, Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, Cape Town, South Africa.
⁷ Department of Psychiatry and Mental Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
⁸ Genetic Care Centre, Tygerberg Academic Hospital, Cape Town, South Africa.
⁹ Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, Cape Town, South Africa.
¹⁰ Department of Pediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.

PMID: 33710528
DOI: 10.1007/s11011-021-00712-9

Review

Pathology-supported genetic testing as a method for disability prevention in multiple sclerosis (MS). Part II. Insights from two MS cases

Susan J van Rensburg et al. Metab Brain Dis. 2021 Aug.

. 2021 Aug;36(6):1169-1181.

doi: 10.1007/s11011-021-00712-9. Epub 2021 Mar 12.

Authors

Affiliations

¹ Division of Chemical Pathology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa. sjvr@sun.ac.za.
² Division of Chemical Pathology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
³ Department of Internal Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg Academic Hospital, Cape Town, South Africa.
⁴ Division of Chemical Pathology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, National Health Laboratory Service (NHLS), Cape Town, South Africa.
⁵ Central Analytical Facility (CAF), DNA Sequencing Unit, Stellenbosch University, Stellenbosch, South Africa.
⁶ Department of Medical Imaging and Therapeutic Sciences, Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, Cape Town, South Africa.
⁷ Department of Psychiatry and Mental Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
⁸ Genetic Care Centre, Tygerberg Academic Hospital, Cape Town, South Africa.
⁹ Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, Cape Town, South Africa.
¹⁰ Department of Pediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.

PMID: 33710528
DOI: 10.1007/s11011-021-00712-9

Erratum in

Correction to: Pathology-supported genetic testing as a method for disability prevention in multiple sclerosis (MS). Part II. Insights from two MS cases.
van Rensburg SJ, Hattingh C, Johannes C, Moremi KE, Peeters AV, van Heerden CJ, Erasmus RT, Zemlin AE, Kemp MC, Jaftha M, Khine AA, Potocnik FCV, Whati L, Engel-Hills P, van Toorn R, Kotze MJ. van Rensburg SJ, et al. Metab Brain Dis. 2021 Aug;36(6):1183-1184. doi: 10.1007/s11011-021-00722-7. Metab Brain Dis. 2021. PMID: 33909201 No abstract available.

Abstract

In Part I of this Review we evaluated the scientific evidence for a Metabolic Model of multiple sclerosis (MS). Part II outlines the implementation of an adaptive pathology-supported genetic testing (PSGT) algorithm aimed at preventing/reversing disability in two illustrative MS cases, starting with a questionnaire-based risk assessment, including family history and lifestyle factors. Measurement of iron, vitamin B12, vitamin D, cholesterol and homocysteine levels identified biochemical deficits in both cases. Case 1, after following the PSGT program for 15 years, had an expanded disability status scale (EDSS) of 2.0 (no neurological sequelae) together with preserved brain volume on magnetic resonance imaging (MRI). A novel form of iron deficiency was identified in Case 1, as biochemical testing at each hospital submission due to MS symptoms showed low serum iron, ferritin and transferrin saturation, while hematological status and erythrocyte sedimentation rate measurement of systemic inflammation remained normal. Case 2 was unable to walk unaided until her EDSS improved from 6.5 to 4.0 over 12 months after implementation of the PSGT program, with amelioration of her suboptimal biochemical markers and changes to her diet and lifestyle, allowing her to regain independence. Genotype-phenotype correlation using a pathway panel of functional single nucleotide variants (SNVs) to facilitate clinical interpretation of whole exome sequencing (WES), elucidated the underlying metabolic pathways related to the biochemical deficits. A cure for MS will remain an elusive goal if separated from nutritional support required for production and maintenance of myelin, which can only be achieved by a lifelong investment in wellness.

Keywords: Biochemical markers; Disability prevention; Multiple sclerosis; Nutritional reserve; Pathology-supported genetic testing (PSGT); Whole exome sequencing (WES).

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References

1. Abbaspour N, Hurrell R, Kelishadi R (2014) Review on iron and its importance for human health. J Res Med Sci 19:164–174 - PubMed - PMC
1. Andronikou S, Ackermann C, Laughton B, Cotton M, Tomazos N, Spottiswoode B, Mauff K, Pettifor JM (2015) Corpus callosum thickness on mid-sagittal MRI as a marker of brain volume: a pilot study in children with HIV-related brain disease and control. Pediatr Radiol 45:1016–1025. https://doi.org/10.1007/s00247-014-3255-y - DOI - PubMed
1. Banwell B, Giovannoni G, Hawkes C, Lublin F (2013) Editors' welcome and a working definition for a multiple sclerosis cure. Mult Scler Relat Disord 2:65–67. https://doi.org/10.1016/j.msard.2012.12.001 - DOI - PubMed
1. Barnett MH, Prineas JW (2004) Relapsing and remitting multiple sclerosis: pathology of the newly forming lesion. Ann Neurol 55:458–468. https://doi.org/10.1002/ana.20016 - DOI - PubMed
1. Bartosik-Psujek H, Psujek M (2019) Vitamin D as an immune modulator in multiple sclerosis. Neurol Neurochir Pol 53:113–122. https://doi.org/10.5603/PJNNS.a2019.0015 - DOI - PubMed

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Pathology-supported genetic testing as a method for disability prevention in multiple sclerosis (MS). Part II. Insights from two MS cases

Affiliations

Pathology-supported genetic testing as a method for disability prevention in multiple sclerosis (MS). Part II. Insights from two MS cases

Authors

Affiliations

Erratum in

Abstract

References

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Medical