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

JIMD Reports
Jirair K BedoyanDouglas Kerr

Abstract

Pyruvate dehydrogenase complex deficiencies (PDCDs) and other mitochondrial disorders (MtDs) can (a) result in congenital lactic acidosis with elevations of blood alanine (Ala) and proline (Pro), (b) lead to decreased ATP production, and (c) result in high morbidity and mortality. 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-specific PDCD due to PDHA1 and PDHB 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-month period. We used the combined Ala:Leu ≥4.0 and Pro:Leu ≥3.0 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...Continue Reading

References

Dec 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·E M KowaloffS J Downing
Aug 1, 1991·Clinical Biochemistry·D S Kerr
Jan 1, 1996·Journal of Inherited Metabolic Disease·B H RobinsonM Ling
Mar 1, 1997·Metabolism: Clinical and Experimental·P W Stacpoole
Mar 12, 2005·Journal of the Neurological Sciences·Ali NainiEric A Schon
Dec 21, 2005·The Journal of Nutrition·Richard A HawkinsJuan R Viña
Feb 5, 2008·Molecular Genetics and Metabolism·UNKNOWN Mitochondrial Medicine Society's Committee on DiagnosisRobert K Naviaux
Apr 29, 2008·Bulletin of the World Health Organization·Anne AndermannVéronique Déry
Jun 19, 2008·Journal of Neurology, Neurosurgery, and Psychiatry·F SedelM Brivet
Jan 13, 2012·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Michael Petros
Mar 8, 2013·Science Translational Medicine·Rosa FerrieroNicola Brunetti-Pierri
Jul 23, 2013·Oncotarget·Rosa Ferriero, Nicola Brunetti-Pierri
Aug 8, 2013·Molecular Genetics and Metabolism·Colleen ClarkeMarni J Falk
Oct 9, 2014·Journal of Bioenergetics and Biomembranes·Tyler G Demarest, Margaret M McCarthy
Oct 31, 2014·Annals of Clinical and Translational Neurology·Rosa FerrieroNicola Brunetti-Pierri
Dec 21, 2014·Journal of Inherited Metabolic Disease·Wolfgang SperlJohannes A Mayr
Jun 18, 2015·Orphanet Journal of Rare Diseases·Sacha FerdinandusseRonald J A Wanders
Jun 26, 2015·Journal of Inherited Metabolic Disease·S Scholl-BürgiD Karall
May 3, 2016·Current Genetic Medicine Reports·Jeffrey R Botkin, Erin Rothwell
Jan 20, 2017·Journal of Inherited Metabolic Disease·Kalliopi SofouNiklas Darin
Apr 28, 2020·Neurology. Genetics·Emanuele BarcaMichio Hirano

❮ Previous
Next ❯

Methods Mentioned

BETA
plasma draw

Software Mentioned

Excel
MassLynx
R Project for

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.