| Summary: | 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
|
|---|
