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With ~140,000 live births annually in Ohio and ~1 in 9,000 overall prevalence of MtDs, we estimate 2 to 3 newborns will have PDCD and 13 to 14 others likely will have another MtD annually. We compared the sensitivities of plasma amino acids (AA) Alanine (Ala), Alanine:Leucine (Ala:Leu), Alanine:Lysine and the combination of Ala:Leu and Proline:Leucine (Pro:Leu), in subjects with known primary\u2010specific PDCD due to <jats:italic>PDHA1<\/jats:italic> and <jats:italic>PDHB<\/jats:italic> mutations vs controls. Furthermore, in collaboration with the Ohio newborn screening (NBS) laboratory, we determined Ala and Pro concentrations in dried blood spot (DBS) specimens using existing NBS analytic approaches and evaluated Ala:Leu and Pro:Leu ratios from DBS specimens of 123,414 Ohio newborns in a 12\u2010month period. We used the combined Ala:Leu \u22654.0 and Pro:Leu \u22653.0 ratio criterion from both DBS and plasma specimens as a screening tool in our retrospective review of newborn data. The screening tool applied on DBS and\/or plasma (or serum) AA specimens successfully identified three unrelated females with novel <jats:italic>de novo<\/jats:italic> <jats:italic>PDHA1<\/jats:italic> mutations, one male with a novel <jats:italic>de novo<\/jats:italic> X\u2010linked <jats:italic>HSD17B10<\/jats:italic> mutation, and a female with <jats:italic>VARS2<\/jats:italic> mutations. This work lays the first step for piloting an NBS protocol in Ohio for identifying newborns at high risk for primary\u2010specific PDCD and other MtDs who might benefit from neonatal diagnosis and early institution of known therapy and\/or potential novel therapies for such disorders.<\/jats:p>","DOI":"10.1002\/jmd2.12153","type":"journal-article","created":{"date-parts":[[2020,8,28]],"date-time":"2020-08-28T09:37:58Z","timestamp":1598607478000},"page":"70-81","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Utility of specific amino acid ratios in screening for pyruvate dehydrogenase complex deficiencies and other mitochondrial disorders associated with congenital lactic acidosis and newborn screening prospects"],"prefix":"10.1002","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9737-6877","authenticated-orcid":false,"given":"Jirair K.","family":"Bedoyan","sequence":"first","affiliation":[{"name":"Departments of Genetics and Genome Sciences Case Western Reserve University (CWRU)  Cleveland Ohio USA"},{"name":"Pediatrics CWRU  Cleveland Ohio USA"},{"name":"Center for Human Genetics University Hospitals Cleveland Medical Center (UHCMC)  Cleveland Ohio USA"},{"name":"Center for Inherited Disorders of Energy Metabolism (CIDEM) UHCMC  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemary","family":"Hage","sequence":"additional","affiliation":[{"name":"Newborn Screening and Radiation Chemistry Ohio Department of Health Laboratory  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ha Kyung","family":"Shin","sequence":"additional","affiliation":[{"name":"School of Medicine CWRU  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Linard","sequence":"additional","affiliation":[{"name":"Newborn Screening and Radiation Chemistry Ohio Department of Health Laboratory  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin","family":"Ferren","sequence":"additional","affiliation":[{"name":"Pediatrics CWRU  Cleveland Ohio USA"},{"name":"Center for Human Genetics University Hospitals Cleveland Medical Center (UHCMC)  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Ducich","sequence":"additional","affiliation":[{"name":"School of Medicine CWRU  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirkland","family":"Wilson","sequence":"additional","affiliation":[{"name":"School of Medicine CWRU  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"April","family":"Lehman","sequence":"additional","affiliation":[{"name":"Nationwide Children's Hospital (NCH) and The Ohio State University College of Medicine Section of Genetic and Genomic Medicine  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori\u2010Anne","family":"Schillaci","sequence":"additional","affiliation":[{"name":"Departments of Genetics and Genome Sciences Case Western Reserve University (CWRU)  Cleveland Ohio USA"},{"name":"Pediatrics CWRU  Cleveland Ohio USA"},{"name":"Center for Human Genetics University Hospitals Cleveland Medical Center (UHCMC)  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kandamurugu","family":"Manickam","sequence":"additional","affiliation":[{"name":"Nationwide Children's Hospital (NCH) and The Ohio State University College of Medicine Section of Genetic and Genomic Medicine  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari","family":"Mori","sequence":"additional","affiliation":[{"name":"Nationwide Children's Hospital (NCH) and The Ohio State University College of Medicine Section of Genetic and Genomic Medicine  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Bartholomew","sequence":"additional","affiliation":[{"name":"Nationwide Children's Hospital (NCH) and The Ohio State University College of Medicine Section of Genetic and Genomic Medicine  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"DeBrosse","sequence":"additional","affiliation":[{"name":"Departments of Genetics and Genome Sciences Case Western Reserve University (CWRU)  Cleveland Ohio USA"},{"name":"Pediatrics CWRU  Cleveland Ohio USA"},{"name":"Center for Human Genetics University Hospitals Cleveland Medical Center (UHCMC)  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Akron Children's Hospital (ACH) Rebecca D. 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