Multiple sclerosis-like diagnosis as a complication of previously treated malaria in an iron and vitamin D deficient Nigerian patient

Abstract

In contrast to malaria, multiple sclerosis (MS) is infrequently found in Black Africans. We describe a 29 year old Nigerian female who developed an MS-like condition with symptoms similar to relapsing-remitting MS following malaria infection, leading to a diagnosis of MS. However, absence of hyperintense lesions in the brain and spinal cord presented a conundrum since not all the diagnostic criteria for MS were met. Pathology supported genetic testing (PSGT) was applied to combine family and personal medical history, lifestyle factors, and biochemical test results for interpretation of genetic findings. This approach provides a means of identifying risk factors for different subtypes of demyelinating disease. The patient was subsequently treated according to an individualised intervention program including nutritional supplementation as well as a change in diet and lifestyle. Deficiencies of vitamin B12, iron and vitamin D were addressed. Genetic analysis revealed absence of the HLA DRB1*1501 allele, considered to be the most prominent genetic risk factor for MS. Extended mutation analysis identified variations in three genes in the folate-vitamin B12 metabolic pathway, which could have increased the patient's sensitivity to the antifolate drugs used to treat the malaria. A glutathione-S-transferase GSTM1 null allele, previously associated with neurological complications of malaria, was also detected. Furthermore, a heterozygous variation in the iron-related transmembrane protease serine 6 (TMPRSS6) gene, rs855791 was found, which could have impacted the patient's iron status following two successive blood donations and exposure to malaria preceding the MS diagnosis. PSGT identifies relevant risk factors for demyelinating disorders resembling MS and uses the data for individualised treatment programs, and to systematically build a database that can provide evidence in large patient cohorts. Follow-up investigations may be suggested, such as whole exome sequencing in selected cases, to ensure that remyelination and restoration of function are achieved.

Identification of an iron-responsive subtype in two children diagnosed with relapsing-remitting multiple sclerosis using whole exome sequencing

“…Variant calling was performed on the TorrentServer against an ethnically concordant major allele reference genome based on Genome Reference Consortium Human Build 37 patch release 13 (GRCh37.p13), NCBI Homo sapiens Annotation Release 105 [50]. Variants were annotated in IonReporter 5.6 and prioritised based on their role in iron deficiency [47,51], by using an in-house pipeline of clinically relevant genes selected from the approximately 20,000 human genes. All variants reported were verified by Sanger sequencing.…”