2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Retrospective evaluation of amino acid ratios for screening and diagnostic utility for pyruvate dehydrogenase complex deficiency(PDCD) and other mitochondrial disorders(MtDs)

Retrospective evaluation of amino acid ratios for screening and diagnostic utility for pyruvate dehydrogenase complex deficiency(PDCD) and other mitochondrial disorders(MtDs)

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This study evaluated the utility of specific amino acid (AA) ratios as biomarkers for pyruvate dehydrogenase complex deficiency (PDCD) and other mitochondrial disorders (MtDs). The researchers reviewed medical records from 11,045 patients and collected data from their first serum/plasma AA analysis. The study included individuals with molecularly and/or enzymatically confirmed diagnoses of inborn errors of metabolism (IEM) as well as individuals with other clinically defined conditions for comparison.<br /><br />The results showed that specific AA ratios, including Ala/Lys and Ala/Leu, efficiently discriminated subjects with PDCD from those with other disorders such as primary MtDs, organic acidemias, and fatty acid oxidation disorders. However, these ratios were not specific for PDCD and could identify other disorders as well. Specific combination ratios of AA ratios were more sensitive in identifying PDCD, with the combination of Ala/Lys ≥3.0 and Ala/Leu ≥5.0 showing the highest sensitivity.<br /><br />The study also compared the incidence of PDCD in different regions. From a pilot newborn screening study, the annual incidence of PDCD was estimated to be at least 1 in 41,000 live births in the United States. The researchers found that approximately 3 cases of PDCD occurred annually in Pennsylvania.<br /><br />Overall, the study suggests that specific AA ratios, especially when used in combination, can be useful biomarkers for the early identification of PDCD in newborn screening. Incorporating these ratios into screening protocols can help identify at-risk newborns and facilitate early interventions with known and novel therapeutics for PDCD. However, further research is needed to improve the specificity of these biomarkers and rule out other disorders.

Asset Subtitle

Presenting Author - Anisha Verma, BS, MS; Co-Author - April N. Lehman, MD,FACMG; Co-Author - Lorna Cropcho, CLA(ASCP); Co-Author - Danielle Black, BS,MS; Co-Author - Steven F. Dobrowolski, PhD; Co-Author - Jerry Vockley, MD, PhD, FACMG; Co-Author - Jirair K. Bedoyan, MD, PhD, FACMG;

Meta Tag

Biochemical genetics

Mitochondria

Therapy

Co-Author April N. Lehman, MD,FACMG

Co-Author Lorna Cropcho, CLA(ASCP)

Co-Author Danielle Black, BS,MS

Co-Author Steven F. Dobrowolski, PhD

Co-Author Jerry Vockley, MD, PhD, FACMG

Co-Author Jirair K. Bedoyan, MD, PhD, FACMG

Presenting Author Anisha Verma, BS, MS

Keywords

amino acid ratios

biomarkers

pyruvate dehydrogenase complex deficiency

mitochondrial disorders

specific AA ratios

Ala/Lys

Ala/Leu

combination ratios

newborn screening

early identification