Galactosemia : the South African study / Phiyani Justice Lebea

• Main Author: Lebea, Phiyani Justice
• Published: North-West University 2009
• Online Access: http://hdl.handle.net/10394/1361

Classic galactosemia and congenital hypothyroidism are both inborn errors of metabolism. The biochemical and molecular detection of both disorders is already defined in scientific literature. Their management is also well documented, yet their detection especially in poorer communities remains uncoordinated moreover in developing countries. These disorders can both be detected early in childhood if neonatal screening is instituted. When diagnosed early in childhood, congenital hypothyroidism can be successfully treated. In the case of classic galactosemia, preliminary clinical outcome is satisfactory although long-term prognosis is disappointing. In South Africa, neonatal screening has not been instituted. The reasons are related to the economics of the country as well as the lack of sufficient data about the prevalence and incidence of the diseases. In this study, a pilot newborn screening program for classic galactosemia and congenital hypothyroidism that take into consideration the socio-economic status of the surveyed populations has been established. The total protocol includes the sampling, storage of sampled specimens, biochemical and molecular diagnostic techniques. Using this protocol, an incidence ratio of one in a thousand congenital hypothyroidism cases was established in the Nkangala region of the Mpumalanga province of South Africa. Appropriate management therapy was also instituted in affected individuals. Furthermore, to initiate a lead into the investigation of mechanistic imperatives that result in poor long-term prognosis of classic galactosemia, a novel approach towards application of RNA interference in disease mechanism study was introduced. In this approach, the design and development of a mammalian cell model with GALT gene knockdown using RNAi was utilized to create a cellular state reminiscent of a classic galactosemia rather than to elucidate the gene function as is conventionally applied. The model was successfully completed and was compatible with the enzymatic activity prerequisites when compared to the control sets. However, the mammalian cellular model still needs to be rigorously tested to confirm its application towards studying long-term biochemical outcomes and identification of galactosemia secondary biomarkers. === Thesis (Ph.D. (Biochemistry))--North-West University, Potchefstroom Campus, 2007