Detection of errors in methylmalonyl-CoA metabolism by using amniotic fluid

Area of Science:

• Biochemistry
• Medical Genetics
• Prenatal Diagnostics

Background:

• Methylmalonic acidemia is a serious inherited metabolic disorder.
• Accurate and timely prenatal diagnosis is crucial for management.
• Existing diagnostic methods can be time-consuming.

Purpose of the Study:

• To develop a rapid prenatal diagnostic method for methylmalonic acidemia.
• To differentiate between vitamin B12-responsive and non-responsive forms.
• To improve diagnostic turnaround time for affected pregnancies.

Main Methods:

• Measuring methylmalonyl-CoA mutase activity in non-cultured amniotic cells.
• Assessing methylmalonate concentration in amniotic fluid.
• Utilizing adenosylcobalamin for enzyme stabilization and methylmalonyl-CoA with high specific activity.

Main Results:

• Accurate diagnosis of vitamin B12-nonresponsive methylmalonic acidemia via low mutase activity and high methylmalonate levels.
• Diagnosis of vitamin B12-responsive form by detecting amniotic fluid methylmalonate with normal cellular mutase activity post-adenosylcobalamin addition.
• Results obtainable within two days.

Conclusions:

• The developed method allows for rapid and accurate prenatal detection of methylmalonic acidemia.
• The assay effectively distinguishes between the two main forms of the disorder.
• This approach offers a significant improvement in prenatal diagnostic speed for methylmalonic acidemia.