Project Details

Monogenic Intestinal Disease in Africa

Zeenat Gaibee, MBChB, FCPaeds, MMED

Summary

BACKGROUND: Monogenic intestinal disorders result in severe and often life-threatening diarrhea and malabsorption in the developing phase of young children’s lives requiring significant medical support. With advances in our understanding of the disease, novel and lifesaving treatments are becoming available from immunomodulation, biologics, stem cell transplant and at times simple changes in diet. GAP: Recently, research disparities have been highlighted in understanding the causes of genetic diseases in Africa and to our knowledge, there have not been any studies exploring monogenic intestinal diseases in Africa. Having an early diagnosis has direct clinical impact particularly in resource limited settings. A clinical and research pipeline is not yet well developed to identify and diagnose monogenic intestinal disease. HYPOTHESIS: Our hypothesis is that children is Africa have a similar incidence of monogenic intestinal disease as children from other parts of the world and that these disorders can be identified using genetic testing. METHODS: Sub-Saharan African patients < 6 years of age presenting with chronic diarrhea, in whom infection, or allergy have been excluded, will be identified through routine clinical care. Next generation sequencing will be processed at the South African Genome Centre (SAMRC). The bioinformatic data and computational processing will be shared between SAMRC and Sick Kids Hospital to inform known and novel mutations and directly fed back to clinical care. Functional validation of novel variants will be explored through the Muise Lab. RESULTS: Pending. IMPACT: We believe this first-in-kind study in African pediatrics will directly impact the clinical practice and outcomes for several children and their families and inform and adjust current palliative practice. It will further assist local clinicians in providing targeted treatments with a clinical and cost benefits. This pilot project will assist with establishment of an Afro-centric program that will allow for a local diagnostic pathway for intestinal disease and contributor the global understanding and future research opportunities.