Testing MMA₁₀₀ - the eGFR-adjusted concentration of methylmalonic acid in plasma

Area of Science:

• Clinical chemistry
• Biomarker analysis
• Renal function assessment

Background:

• Plasma methylmalonic acid (MMA) concentration is elevated in cobalamin deficiency (CD).
• MMA levels also increase with declining glomerular filtration rate (GFR), confounding CD diagnosis.
• Renal function must be considered when interpreting MMA values.

Purpose of the Study:

• To compare the performance of MMA adjusted for estimated GFR (eGFR) to 100 mL/min/1.73 m² (MMA100) against unadjusted MMA.
• To evaluate MMA100 and MMA based on their relationship with eGFR, diagnostic accuracy, and age-specific reference limits.

Main Methods:

• Utilized a large clinical dataset to analyze MMA and MMA100.
• Assessed the correlation between MMA/MMA100 and eGFR.
• Compared the diagnostic accuracy of MMA/MMA100 for cobalamin deficiency.
• Determined and compared upper reference limits for MMA/MMA100 across different age groups.

Main Results:

• MMA100 demonstrated a weaker relationship with eGFR compared to unadjusted MMA.
• MMA100 exhibited higher diagnostic accuracy for cobalamin deficiency than MMA.
• Upper reference limits for MMA100 showed less variation with age than those for MMA.

Conclusions:

• MMA100 is a more robust biomarker for cobalamin deficiency than MMA.
• Adjusting MMA for renal function enhances its utility in diagnosing cobalamin deficiency.