Glutaric acidaemia type II (multiple acyl-CoA dehydrogenation deficiency)

Area of Science:

• Biochemistry
• Molecular Biology
• Genetics

Background:

• Glutaric acidaemia type II (GAII) is a metabolic disorder.
• The disorder is linked to defects in electron transfer from FAD-containing dehydrogenases to the respiratory chain.
• Electron transfer flavoprotein (ETF) and ETF dehydrogenase are key proteins in this pathway.

Purpose of the Study:

• To investigate the specific defect in electron transfer in GAII patients.
• To determine if ETF dehydrogenase is implicated in the GAII phenotype.

Main Methods:

• Purification of ETF and ETF dehydrogenase.
• Preparation of antisera against ETF and ETF dehydrogenase.
• SDS-PAGE electrophoresis of mitochondrial membranes from a GAII infant.
• Electron Paramagnetic Resonance (EPR) spectroscopy of mitochondrial membranes.

Main Results:

• No cross-reactive material for ETF dehydrogenase was detected in GAII infant mitochondrial membranes using specific antiserum.
• EPR spectroscopy showed a significant decrease in the ETF dehydrogenase signal in the same membranes.
• These findings indicate a deficiency in ETF dehydrogenase in the affected infant.

Conclusions:

• The study suggests that defects in electron transfer flavoprotein dehydrogenase are a cause of glutaric acidaemia type II in some patients.
• This points to a specific role for ETF dehydrogenase in the respiratory chain dysfunction observed in GAII.