Genetic diseases
Genetic diseases
Abnormal hemoglobins and thalassemia
Our early studies on genetic diseases concerned the hemoglobinopathies, which consist of two types. Thalassemia results from the lack or decreased synthesis of hemoglobin chains, with α-thalassemia and β-thalassemia occurring with high frequency in Thailand, at 20% and 10% respectively. Abnormal hemoglobins have mutations altering the structure of a globin chain: they are usually rare, but some occur at high frequency, such as Hb E [β26 Glu-Lys] which can rise to 53% frequency in the Northeast. We have studied both thalassemias and abnormal hemoglobins in collaboration with Professor Suthat Fucharoen at Mahidol University, and characterized 10 out of the 30 or more abnormal hemoglobins found in Thailand. Since hemoglobinopathies are now well characterized in Thailand, we turned our attention to other genetic diseases.
Inborn Errors of Metabolism
Inborn errors of metabolism arise from deficiencies of enzymes in metabolic pathways, such as amino acid metabolism and macromolecule degradation. They are often detected by an accumulation of the substrate and/or a decrease in the metabolic products of the 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. Some cause severe clinical manifestations, such as mental retardation or developmental abnormalities, but sometimes, devastating effects can be avoided through proper treatment, so early detection is important.
We collaborate with pediatricians in Bangkok, including Siriraj Hospital and Ramathibodi Hospital at Mahidol University, to analyze the levels of deficient enzymes and detect mutant genes causing the diseases. A major interest includes lysosomal storage diseases, such as Pompe disease, Fabry disease, Gaucher disease, Hurler Syndrome and Hunter Syndrome, where enzyme deficiency causes accumulation of substances leading to organ damage and physical defects. Information on mutations are useful for genetic counseling, and assist in early diagnosis, which is important in enabling treatment to be carried out early enough to prevent the effects of the disease. We also study methylmalonic acidemia (MMA), caused by defective function of vitamin B12-dependent enzyme methylmalonyl CoA mutase, due to defects in mutase enzyme itself or in coenzyme metabolism. In both cases, many mutations are unique to Thailand, so need to be studied locally. Growing evidence reveals that some patients with Parkinson’s disease carry a heterozygous state of glucocerebrosidase (GBA) gene mutation (Gaucher disease carrier). This leads to the hypothesis that GBA mutations in the heterozygous state may contribute as a genetic risk factor for sporadic Parkinson’s disease. We are also studying the GBA mutations in association with Parkinson’s disease using the proteomic approach.
