van Rensburg Susan J, van Toorn Ronald, Moremi Kelebogile E, Peeters Armand V, Oguniyi Adesola, Kotze Maritha J
Chemical Pathology, National Health Laboratory Service (NHLS) and Stellenbosch University, Cape Town, South Africa.
Paediatric Medicine and Child Health, Stellenbosch University, Cape Town, South Africa.
Metab Brain Dis. 2016 Feb;31(1):197-204. doi: 10.1007/s11011-015-9788-4. Epub 2016 Jan 8.
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.
与疟疾不同,多发性硬化症(MS)在非洲黑人中很少见。我们描述了一名29岁的尼日利亚女性,她在感染疟疾后出现了类似MS的病症,症状类似于复发缓解型MS,最终被诊断为MS。然而,由于未满足MS的所有诊断标准,大脑和脊髓中缺乏高强度病变这一情况带来了难题。应用病理学支持的基因检测(PSGT)来综合家族和个人病史、生活方式因素以及生化检测结果,以解读基因发现。这种方法提供了一种识别不同亚型脱髓鞘疾病风险因素的手段。该患者随后接受了个体化干预方案的治疗,包括营养补充以及饮食和生活方式的改变。解决了维生素B12、铁和维生素D的缺乏问题。基因分析显示不存在HLA DRB1*1501等位基因,该等位基因被认为是MS最主要的遗传风险因素。扩展突变分析确定了叶酸 - 维生素B12代谢途径中三个基因的变异,这可能增加了患者对用于治疗疟疾的抗叶酸药物的敏感性。还检测到一个谷胱甘肽 - S - 转移酶GSTM1无效等位基因,该等位基因先前与疟疾的神经并发症有关。此外,发现铁相关跨膜蛋白酶丝氨酸6(TMPRSS6)基因rs855791存在杂合变异,这可能在两次连续献血以及MS诊断前接触疟疾后影响了患者的铁状态。PSGT识别出类似于MS的脱髓鞘疾病的相关风险因素,并将这些数据用于个体化治疗方案,以及系统地建立一个可为大量患者队列提供证据的数据库。可能建议进行后续调查,例如对选定病例进行全外显子测序,以确保实现髓鞘再生和功能恢复。