Dr. Oleg Shchelochkov at BBCon 2024
Breath Analysis for Biomarker Discovery and Outcome Stratification in Propionic Acidemia
00:00 – Introductions
01:36 – Presentation: ‘Breath Analysis for Biomarker Discovery and Outcome Stratification in Propionic Acidemia’
17:00 – Q&A
Talk Abstract:
Background: Impaired oxidation of branched chain amino acids may give rise to volatile organic compounds (VOCs). We hypothesized that VOCs will be present in exhaled breath of participants with propionic acidemia (PA), and their relative abundance would correlate with characteristics of the disease.
Methods: We enrolled 5 affected participants from a natural history study of PA (ClinicalTrials.gov ID NCT02890342) plus five age- and sex-matched unaffected controls. We collected exhaled breath using a non-invasive breath sampling platform paired with thermal desorption-gas chromatography-mass spectrometry. Clinical and biochemical parameters were correlated with the relative abundance of VOCs.
Results: Unbiased screening identified several candidate VOC biomarkers of PA. One candidate putatively identified as 3-pentanone was the most abundant (45-fold higher in cases vs. controls, p-value < 0.05). 3-Pentanone abundance positively correlated with plasma propionylcarnitine (p = 0.01), plasma 2-methylcitrate (p < 0.05), 3-OH-propionate (p < 0.01), full scale IQ (p < 0.01), and showed a statistical trend with height z-scores (p = 0.08). It inversely correlated with the whole-body in vivo oxidation of 1-13C-propionate (p < 0.05). In a participant who received an orthotopic liver transplant, 3-pentanone levels were lower and segregated with “mild” PA.
Conclusion: Non-invasive breath sampling is a promising method to identify and quantitate VOCs that correlate with the clinical and biochemical parameters of PA. Our proof-of-principle findings may have wide implications for the diagnosis and severity stratification of inborn errors of metabolism affecting oxidation of amino acids which might be monitored in a similar fashion.
Speaker Biography:
Dr. Oleg Shchelochkov is a board-certified pediatrician, clinical geneticist and medical biochemical geneticist, and is currently an associate investigator at NHGRI. After his early pediatrics training at the University of Iowa and genetics training at Baylor College of Medicine, Dr. Shchelochkov was a tenure-track assistant professor within the Pediatrics Department and Division of Genetics at the University of Iowa Hospitals and Clinics. He has been part of the NHGRI research community since 2015, starting as a staff clinician. Until recently, he was an associate research-physician studying many aspects of organic acidemias. In 2021, NHGRI appointed Dr. Shchelochkov as the new Director of Clinical and Laboratory Residencies and Fellowships. Dr. Shchelochkov is an author and a co-author on more than 60 peer-reviewed publications and book chapters.
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