Maple syrup urine disease: mutation analysis in Turkish patients

Area of Science:

• Biochemistry
• Genetics
• Metabolic Disorders

Background:

• Maple syrup urine disease (MSUD) is an organic acidaemia, prevalent in Turkey.
• It results from impaired branched-chain keto acid dehydrogenase (BCKAD) enzyme complex activity.

Purpose of the Study:

• To investigate mutations in the BCKAD complex genes (E1alpha, E1beta, E2) in Turkish MSUD patients.
• To identify novel mutations and polymorphisms associated with MSUD.

Main Methods:

• Mutation analysis of E1alpha, E1beta, and E2 genes in 12 Turkish MSUD patients.
• Identification and characterization of novel mutations and polymorphisms.

Main Results:

• Three novel missense mutations (Q80E, C213Y, T106M) and one polymorphism (F280F) were found in the E1alpha gene.
• A novel splice site mutation (IVS3 - 1G>A) was identified in the E2 gene.
• Homozygous mutations, including the splice site mutation, caused classical MSUD. One patient presented compound heterozygosity for mutations in two different genes.

Conclusions:

• Novel mutations in E1alpha and E2 genes contribute to MSUD in the Turkish population.
• The IVS3 - 1G>A splice site mutation in E2 affects protein structure and function.
• Genetic heterogeneity exists in MSUD, with potential for compound heterozygosity.