DBT Gene Mutation Among Maple Syrup Urine Disease (MSUD) In Malaysian Population
Total Views: 186 | Total Downloads: 151
Keywords:Maple syrup urine disease, MSUD, BCAA, DBT gene, founder mutation
Maple syrup urine disease (MSUD) is an autosomal recessive genetic disease and an inherited autosomal recessive trait. It is characterised by a deficiency of an enzyme complex, resulting in an excess of branched-chain amino acids (BCAAs), which are toxic to the nervous system. Our four cases generally presented with lethargy and poor feeding weeks after birth. They were all treated for sepsis until the laboratory results showed high levels of BCAAs, which indicated MSUD. Genetic analysis showed that the four cases were homozygous for the DBT gene mutation c.1196C>G (p.S399C), a possible founder mutation. All of our cases were managed accordingly, with regular monitoring of the BCAA levels. Dietary support, with infant formulas free of BCAAs, was provided to all four cases with regular follow-up at the paediatric genetic clinic. All cases had spastic diplegic and developmental delays.
Pramitasari, P.A., I.G.L. Sidiartha, and I. Widodo, Maple syrup urine disease: the first case in Bali. Bali Medical Journal, 2018. 7(1): p. 240-243.
Idrees, Z., et al., Classic Maple Syrup Urine Disease In A 46-Day-Old Baby: A Case Report. Khyber Medical University Journal, 2018. 10(1).
Dr.N.L.N.Moorthy, D.V., Dr. K. Priyanka, Maple Syrup Urine Disease: A Case Report. IOSR Journal of Dental and Medical Sciences (IOSR-JDMS) 2015. Volume 14(Issue 10): p. PP 22-24.
Blackburn, P.R., et al., Maple syrup urine disease: mechanisms and management. The application of clinical genetics, 2017. 10: p. 57.
Yunus, Z.M., et al., Clinical and biochemical profiles of maple syrup urine disease in Malaysian children, in JIMD Reports-Case and Research Reports, 2012/2. 2011, Springer. p. 99-107.
Chace, D.H. and E.W. Naylor, Expansion of newborn screening programs using automated tandem mass spectrometry. Mental Retardation and Developmental Disabilities Research Reviews, 1999. 5(2): p. 150-154.
Chace, D.H., T.A. Kalas, and E.W. Naylor, The application of tandem mass spectrometry to neonatal screening for inherited disorders of intermediary metabolism. Annual review of genomics human genetics, 2002. 3(1): p. 17-45.
Rashed, M.S., Z. Rahbeeni, and P.T. Ozand. Application of electrospray tandem mass spectrometry to neonatal screening. in Seminars in perinatology. 1999. Elsevier.
Ali, E.Z. and L.H. Ngu, Fourteen new mutations of BCKDHA, BCKDHB and DBT genes associated with maple syrup urine disease (MSUD) in Malaysian population. Molecular Genetics and Metabolism Reports, 2018. 17: p. 22-30.
Silao, C.L.T., C.D. Padilla, and M. Matsuo, A novel deletion creating a new terminal exon of the dihydrolipoyl transacylase gene is a founder mutation of Filipino maple syrup urine disease. Molecular Genetics and Metabolism, 2004. 81(2): p. 100-104.
Chi, C.S., et al., Maple syrup urine disease in the Austronesian aboriginal tribe Paiwan of Taiwan: A novel DBT (E2) gene 4.7 kb founder deletion caused by a nonhomologous recombination between LINE-1 and Alu and the carrier-frequency determination. European Journal of Human Genetics, 2003. 11(12): p. 931-936.
Puffenberger, E. Genetic heritage of the Old Order Mennonites of southeastern Pennsylvania. in American Journal of Medical Genetics Part C: Seminars in Medical Genetics. 2003. Wiley Online Library.
Quental, S., et al., Revisiting MSUD in Portuguese Gypsies: Evidence for a founder mutation and for a mutational hotspot within the BCKDHA gene. Annals of Human Genetics, 2009. 73(3): p. 298-303.
Edelmann, L., et al., Maple syrup urine disease: Identification and carrier-frequency determination of a novel founder mutation in the Ashkenazi Jewish population. American Journal of Human Genetics, 2001. 69(4): p. 863-868.
Chuang, J. L., Cox, R. P., & Chuang, D. T. (1997). E2 transacylase-deficient (type 2) maple syrup urine disease. Aberrant splicing of E2 mRNA caused by internal intronic deletions and association with thiamine-responsive phenotype. The Journal of clinical investigation, 100(3), 736-744.
Narayanan, M. P., Menon, K. N., & Vasudevan, D. M. (2013). Analysis of gene mutations among South Indian patients with maple syrup urine disease, identification of four novel mutations.
Campanholi, D. R. R., Margutti, A. V. B., Silva Jr, W. A., Garcia, D. F., Molfetta, G. A., Marques, A. A., ... & Camelo Jr, J. S. (2021). Molecular basis of various forms of maple syrup urine disease in Chilean patients. Molecular Genetics & Genomic Medicine, e1616.
How to Cite
Copyright (c) 2021 Che Soh N.A.A et al.
This work is licensed under a Creative Commons Attribution 4.0 International License.
The copyright of this article will be vested to author(s) and granted the journal right of first publication with the work simultaneously licensed under the Creative Commons Attribution 4.0 International (CC BY 4.0) license, unless otherwise stated.