Clinical, Biochemical, Molecular, and Therapeutic Analysis of Maple Syrup Urine Disease in Upper Egypt

Abstract

Maple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disorder caused by mutations in any of the genes encoding for the branched-chain keto dehydrogenase (BCKDH) components. This study screened MSUD patients throughout the whole Upper Egypt describing their symptoms, clinical and laboratory findings, genetic studies, and their treatment, with a 6-month follow-up for their responses. Screening identified three children with MSUD. Homozygous mutation in R195Q single nucleotide polymorphism (SNP) within the BCKDHA gene was found with the second MSUD patient. Follow-up for 6 months to assess the treatment regimens and progression of cases demonstrated that early treatment regimens including a dietary restriction of branched-chain amino acids with L-Carnitine administration could prevent MSUD-associated intellectual disabilities. It was concluded that R195Q SNP is pathogenic, and it may cause inherited forms of MSUD in some patients. MSUD cases have rarely been reported; so these findings will be highly useful for future cases of MSUD in the Upper Egyptian population.

Keywords

MSUD - L-carnitine - R195Q

Publication History

Received: 07 May 2020

Accepted: 22 June 2020

Article published online:
10 August 2020

• References

• 1 Illsinger S, Schmidt KH, Lücke T, Vaske B, Bohnhorst B, Das AM. Plasma and urine amino acid pattern in preterm infants on enteral nutrition: impact of gestational age. Amino Acids 2010; 38 (03) 959-972
• 2 Hou JW, Hwang TL. Different gene preferences of maple syrup urine disease in the aboriginal tribes of Taiwan. Pediatr Neonatol 2014; 55 (03) 213-217
• 3 Nellis MM, Kasinski A, Carlson M. et al. Relationship of causative genetic mutations in maple syrup urine disease with their clinical expression. Mol Genet Metab 2003; 80 (1-2): 189-195
• 4 Puffenberger EG. Genetic heritage of the Old Order Mennonites of southeastern Pennsylvania. Am J Med Genet C Semin Med Genet 2003; 121C (01) 18-31
• 5 Chuang DT, Chuang JL, Wynn RM. Lessons from genetic disorders of branched-chain amino acid metabolism. J Nutr 2006; 136 (01) 243S-249S
• 6 Hassan FA, El-Mougy F, Sharaf SA. et al. Inborn errors of metabolism detectable by tandem mass spectrometry in Egypt: the first newborn screening pilot study. J Med Screen 2016; 23 (03) 124-129
• 7 Wang XL, Li CJ, Xing Y, Yang YH, Jia JP. Hypervalinemia and hyperleucine-isoleucinemia caused by mutations in the branched-chain-amino-acid aminotransferase gene. J Inherit Metab Dis 2015; 38 (05) 855-861
• 8 Strauss KA, Wardley B, Robinson D. et al. Classical maple syrup urine disease and brain development: principles of management and formula design. Mol Genet Metab 2010; 99 (04) 333-345
• 9 Lang CH, Lynch CJ, Vary TC. BCATm deficiency ameliorates endotoxin-induced decrease in muscle protein synthesis and improves survival in septic mice. Am J Physiol Regul Integr Comp Physiol 2010; 299 (03) R935-R944
• 10 Blackburn PR, Gass JM, Vairo FPE. et al. Maple syrup urine disease: mechanisms and management. Appl Clin Genet 2017; 10: 57-66
• 11 Liu G, Ma D, Hu P. et al. A novel whole gene deletion of BCKDHB by Alu-mediated non-allelic recombination in a Chinese patient with maple syrup urine disease. Front Genet 2018; 9: 145
• 12 Han B, Han B, Guo B, Liu Y, Cao Z. Two novel mutations in the BCKDHB gene that cause maple syrup urine disease. Pediatr Neonatol 2018; 59 (05) 515-519
• 13 van Calcar S. Nutrition management of maple syrup urine disease. Nutrition Management of Inherited Metabolic Diseases J 2015; 173-183
• 14 Knerr I, Weinhold N, Vockley J, Gibson KM. Advances and challenges in the treatment of branched-chain amino/keto acid metabolic defects. J Inherit Metab Dis 2012; 35 (01) 29-40
• 15 Safdarian E, Galehdari H, Jafarian V. et al. A novel mutation in the BCKDHB gene causes in an Iranian child classic maple syrup urine disease. Zahedan J Res Med Sci 2016; 18 (10) e3399 DOI: 10.17795/zjrms-3399.