Mseleni Joint Disease

As a post doctoral student in South Africa at the University of the Witwatersrand I began to explore this disease, this started with my colleagues and I writing a review paper “Mseleni joint disease: a potential model of epigenetic chrondroplasia”. Within this article we summarise and review the research that has been conducted on MJD and its potential aetiologies, at the end potential future avenues are proposed. Find below, an abbreviated summary of MJD and why the search for its aetiology should continue.

Figure 1. Map of Maputaland South Africa (modified from Figure 1.2, Ceruti 1999 [23]).

Mseleni joint disease (MJD) is a crippling endemic osteoarthritis geographically confined to an area in the Maputaland region in KwaZulu Natal, South Africa. In this isolated region this rare condition only affects people from a Bantu-speaking background and mainly of the Zulu culture, although the people of Mseleni are neither culturally nor genetically different from other such peoples of South Africa (Nurse et al., 1974). MJD is a bilateral uniform arthropathy of the joints most severely localised to the hip. Two studies have examined the incidence of MJD and found that until the age of 10 both sexes are equally affected, and in the adults 32-39% of the females and 10-11% of the males in the community are affected with this condition (Fellingham et al., 1973; Yach and Botha, 1981). MJD is more prominent in females; this may be accounted for by various factors, men being migratory labourers and cultural labour allocation between the sexes. Several sources for the aetiology of Mseleni have been examined; environmental (soil, food, and water); geographic (climate and geology); diet (food, water, palm wine, preparation methods [fire wood and utensils], and nutritional deficiencies [vitamin and mineral]); autoimmunity; infectious agents; and genetics (genetic inheritance, collagen, serogenetics, and biochemical markers). Despite these avenues of research the aetiology for the condition remains unknown. MJD has a continuing socio-economic impact on this community. It is a debilitating disease making daily chores difficult if not impossible depending on the severity of the condition. Many of the members here rely on their land for subsistence, thus, MJD suffers depend on other family members for their survival. As a result this debilitating condition is having a direct impact on the young people in the community because rather than attending school they are helping with subsistence. In the long run this will have a further impact on the whole community. Studies have shown that conditions like MJD affect the entire household and community as a whole (Mann 1984; McLaren et al. 1987). Despite extensive research into those affected with MJD and the environment around them, many people continue to live with this severely crippling condition. Surgical intervention has improved the lives of some, until the aetiology is known, the disease cannot be prevented.

Figure 2. A pelvic radiograph from a patient with MJD

The aetiology of MJD does not seem to be simple, but rather multi-factorial in character. As the condition does not affect all those living in the area (Schnitzler et al., 1987) and with the lack of evidence for Mendelian inheritance, epigenetic changes in response to environmental stimuli may be responsible. Epigenetics is studied through examining chemical modifications in DNA (due to alterations in DNA methylation and/or histones) that do not change one’s genotype, however, they change the phenotypic expression (RNA) of the available genes. Examining genes or proteins involved in the regulation of healthy bone, collagen and cartilage development should be the target approach to chrondroplasia’s with unknown aetiology.

As part of a collaborative team of researchers from UNB, Wits, Yale and the Mseleni Hospital in summer 2013 I went to Mseleni to draw bloods from patients suffering from this disease. The objective is to conduct a preliminary study on a sample of MJD sufferers to isolate genetic targets or alterations in MJD sufferers to be further studied in their relationship to the aetiology of MJD. Analysing the genetics from this perspective allows for the examination of mutations and altered expression of the normal genome, these alterations and targets can then be analysed more specifically to determine what environmental constraints can lead to this. This will be accomplished by whole genomic (DNA) sequencing and whole expression of that sequence (RNA) from patients who suffer with MJD. Until we have an understanding of the aetiology for MJD we cannot begin to effectively treat and prevent it.

Figure 3. A pelvic radiograph from another patient with MJD

Ethics for this research has been obtained through the University of New Brunswick (2013-047); Yale University (#120100962); and the University of the Witwatersrand (M130549).  This work is being conducted with permission and dissemination of results through the South African Provincial and District Health Authorities.