Screening for Methylmalonic and Propionic Acidemia: Clinical Outcomes and Follow-Up Recommendations

Area of Science:

• Biochemistry
• Genetics
• Pediatrics

Background:

• Elevated propionylcarnitine (C3) in newborn screening can indicate serious metabolic disorders.
• Acquired vitamin B12 deficiency is a differential diagnosis for elevated C3, often classified as a false positive.
• Accurate diagnosis is crucial for timely intervention in newborns.

Purpose of the Study:

• To summarize newborn screening data for elevated C3 in Wisconsin (2013-2019).
• To evaluate the effectiveness of second-tier testing in diagnosing inborn errors of metabolism and vitamin B12 deficiency.
• To assess the categorization of false positive screens.

Main Methods:

• Retrospective review of newborn screening data (first- and second-tier tests) for elevated C3.
• Compilation of confirmatory test results.
• Clinical review and categorization of cases into inborn errors of metabolism, maternal/infant B12 deficiency, or false positive.

Main Results:

• Significant overlap observed in biomarker concentrations between genetic and acquired conditions.
• Confirmatory testing revealed incomplete assessment of maternal vitamin B12 status.
• The study identified challenges in differentiating between genetic and acquired causes of elevated C3.

Conclusions:

• Current newborn screening methods show biomarker overlap, complicating the diagnosis of elevated C3.
• Improved ascertainment of maternal vitamin B12 status is needed.
• A refined confirmatory testing algorithm is recommended for accurate diagnosis of inborn errors of metabolism and acquired B12 deficiency.