Thiamine response in maple syrup urine disease.

Area of Science:

• Biochemistry
• Metabolic Disorders
• Genetics

Background:

• Maple syrup urine disease (MSUD) is a rare inherited metabolic disorder.
• It is characterized by the inability to metabolize branched-chain amino acids (BCAAs) and their alpha-ketoacid analogues.
• Thiamine (vitamin B1) is a cofactor for the branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex.

Purpose of the Study:

• To assess the biochemical response of MSUD patients to pharmacologic doses of thiamine.
• To correlate patient response to thiamine with their BCKDH enzyme activity.
• To evaluate the potential of thiamine supplementation as a therapeutic strategy for MSUD.

Main Methods:

• Measured plasma and urinary concentrations of BCAAs and their ketoacid analogues in four MSUD patients.
• Assessed BCKDH enzyme activity in mononuclear blood cells and cultured skin fibroblasts.
• Correlated biochemical marker changes with BCKDH activity before and after thiamine administration.

Main Results:

• Observed a linear correlation between plasma BCAA and ketoacid analogue concentrations.
• Found renal tubular reabsorption of BCAAs and ketoacids to be nearly complete at physiologic concentrations.
• Three out of four patients responded to thiamine, showing reduced BCAA and ketoacid levels.
• Responders exhibited at least 5% of normal BCKDH activity.

Conclusions:

• Thiamine responsiveness in MSUD patients is linked to residual BCKDH enzyme activity.
• Suggests assessing BCKDH activity can predict thiamine treatment efficacy.
• Proposes quantifying plasma BCAA levels before and after thiamine supplementation to assess treatment response in MSUD children.