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

• Published in: Metabolic brain disease 2021-08, Vol.36 (6), p.1169-1181
• Main Authors: van Rensburg, Susan J., Hattingh, Coenraad, Johannes, Clint, Moremi, Kelebogile E., Peeters, Armand V., van Heerden, Carel J., Erasmus, Rajiv T., Zemlin, Annalise E., Kemp, Merlisa C., Jaftha, Mariaan, Khine, Aye Aye, Potocnik, Felix C.V., Whati, Lindiwe, Engel-Hills, Penelope, van Toorn, Ronald, Kotze, Maritha J.
• Format: Article
• Language: English
• Subjects: Algorithms; Biochemical markers; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cholesterol; Erythrocyte sedimentation rate; Erythrocytes; Ferritin; Genetic screening; Genetic testing; Genetic Testing - methods; Genetics; Genotypes; Homocysteine; Humans; Inflammation; Iron; Iron - metabolism; Iron Deficiencies - metabolism; Iron deficiency; Life Style; Magnetic resonance imaging; Metabolic Diseases; Metabolic pathways; Metabolism; Multiple sclerosis; Multiple Sclerosis - diagnosis; Multiple Sclerosis - genetics; Multiple Sclerosis - pathology; Myelin; Myelin Sheath - metabolism; Myelin Sheath - pathology; Neuroimaging; Neurological complications; Neurology; Neurosciences; Nucleotides; Nutrient deficiency; Oncology; Pathology; Phenotypes; Review Article; Risk assessment; Transferrin; Transferrins; Vitamin B12; Vitamin D
• ISSN: 0885-7490; 1573-7365
• DOI: 10.1007/s11011-021-00712-9

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.