Mayo Clinic laboratory and pathology research roundup: January 25

By Samantha Rossi • January 25, 2021

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The research roundup provides an overview of the past week’s research from Mayo Clinic Laboratories consultants, including featured abstracts and a complete list of published studies and reviews.

Featured Abstract

Circulating markers of NADH-reductive stress correlate with mitochondrial disease severity.

Mitochondrial disorders represent a large collection of rare syndromes that are difficult to manage both because we do not fully understand biochemical pathogenesis and because we currently lack facile markers of severity. The m.3243A>G variant is the most common heteroplasmic mitochondrial DNA mutation and underlies a spectrum of diseases, notably mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes (MELAS). To identify robust circulating markers of m.3243A>G disease, we first performed discovery proteomics, targeted metabolomics, and untargeted metabolomics on plasma from a deeply phenotyped cohort (102 patients, 32 controls). In a validation phase, we measured concentrations of prioritized metabolites in an independent cohort using distinct methods. We validated 20 analytes (1 protein, 19 metabolites) that distinguish patients with MELAS from controls. The collection includes classic (lactate, alanine) and more recently identified (GDF-15, α-hydroxybutyrate) mitochondrial markers. By mining untargeted mass-spectra we uncovered 3 less well-studied metabolite families: N-lactoyl-amino acids, β-hydroxy acylcarnitines, and β-hydroxy fatty acids. Many of these 20 analytes correlate strongly with established measures of severity, including Karnofsky status, and mechanistically, nearly all markers are attributable to an elevated NADH/NAD+ ratio, or NADH-reductive stress. Our work defines a panel of organelle function tests related to NADH-reductive stress that should enable classification and monitoring of mitochondrial disease. Via Journal of Clinical Investigation

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Published to PubMed This Week

• Association between paraneoplastic rhombencephalitis and hypertrophic olivary degeneration.
  Journal of Neurology, Neurosurgery, and Psychiatry
• Kidney microstructural features at the time of donation predict long-term risk of chronic kidney disease in living kidney donors.
  Mayo Clinic Proceedings
• Papillary thyroid carcinoma BRAF immunopositivity.
  Mayo Clinic Proceedings
• In reply - micro-thrombosis, perfusion defects, and worsening oxygenation in COVID-19 patients: A word of caution on the use of convalescent plasma.
  Mayo Clinic Proceedings
• Video quality using outpatient smartphone videos in epilepsy: Results from the OsmartViE study.
  European Journal of Neurology
• Error simulation modeling to assess the effects of bias and precision on bilirubin measurements used to screen for neonatal hyperbilirubinemia.
  Clinical Chemistry and Laboratory Medicine
• Hemolytic disease and reticulocytopenia of the newborn attributable to maternal immunoglobulin G anti-M reacting optimally at cold temperatures.
  Transfusion
• Percutaneous catheter drainage of uncomplicated amoebic liver abscess: prospective evaluation of a clinical protocol for catheter removal and the significance of residual collections.
  Abdominal Radiology
• Revisiting the effects of spectral interfering substances in optical end-point coagulation assays.
  International Journal of Laboratory Hematology
• A population-based study of genes previously implicated in breast cancer.
  New England Journal of Medicine

Samantha Rossi

Samantha Rossi is a Digital Marketing Manager at Mayo Clinic Laboratories. She supports marketing strategies for product management and specialty testing. Samantha has worked at Mayo Clinic since 2019.