Genetic Diseases found in Thailand

30 Jan 2023

Our early studies on genetic diseases, since 1987 and earlier, focused on the hemoglobinopathies, which occur frequently in Thailand and consist of two types. Thalassemia results from lack or decreased synthesis of one or more globin chains, while abnormal hemoglobins consist of mutations altering the amino acid sequence of globin chain(s). However, as research in the hemoglobinopathies developed in Thailand, we shifted our interest to Inborn Errors of Metabolism, which can cause severe clinical manifestations, such as mental retardation or developmental abnormalities.

Generally, inborn errors arise from deficiencies in enzymes of various metabolic pathways, such as the urea cycle, pathways for degradation or synthesis of specific amino acids, or mucopolysaccharide degradation. Such disorders may be due to mutations leading to dysfunctional or poorly functioning enzyme or may result from lowered expression or absence of these enzymes. Such enzyme deficiencies are typically detected by an accumulation of the substrate of the enzyme reaction and/or a decrease in the level of metabolites, which occur after the enzyme reaction. Typically, each inborn error of metabolism occurs with low frequency, but there are many defects, so cumulatively, inborn errors of metabolism are significant problems. In many cases, the devastating effects can be avoided through proper treatment, such as in phenylketonuria, which may be treated with diets low in phenylalanine.  So, it is important to detect inborn errors early, and in many countries, newborn screening for selected inborn errors of metabolism is routine.

Many inborn errors of metabolism have also been found in Thailand. We began our studies of inborn errors of metabolism about 30 years ago, and collaborate with medical doctors, especially those at the Faculty of Medicine Siriraj Hospital and the Faculty of Medicine Ramathibodi Hospital at Mahidol University, and with the Queen Sirikit National Institute of Child Health, Ministry of Public Health. Typically, this involves enzyme analysis and genetic testing. The information obtained from our studies are useful for genetic counseling and early diagnosis, that is important in enabling treatment to be carried out early to prevent the effects of the disease. Interestingly, in many cases, the mutations found in Thailand are novel mutations, not previously found in other populations, so functional studies of novel pathogenic mutations are also performed to investigate the cause of the defect. However, each disease represents a whole research field, so we have limited our work to a number of inborn errors of metabolism, such as Methylmalonic acidemia, Gaucher disease, Hurler Syndrome, Hunter Syndrome, Pompe disease, Fabry disease, GM1 gangliosidosis, Isovaleric acidemia and Morquio B syndrome. Study of each disease at molecular level requires significant scientific input in terms of using specific substrates for enzyme assay, synthesizing suitable probes and performing DNA sequence analysis.



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