PMID- 37099687
OWN - NLM
STAT- MEDLINE
DCOM- 20230602
LR  - 20230625
IS  - 1530-8561 (Electronic)
IS  - 0009-9147 (Linking)
VI  - 69
IP  - 6
DP  - 2023 Jun 1
TI  - Methodologies in Mitochondrial Testing: Diagnosing a Primary Mitochondrial 
      Respiratory Chain Disorder.
PG  - 564-582
LID - 10.1093/clinchem/hvad037 [doi]
AB  - BACKGROUND: Mitochondria are cytosolic organelles within most eukaryotic cells. 
      Mitochondria generate the majority of cellular energy in the form of adenosine 
      triphosphate (ATP) through oxidative phosphorylation (OxPhos). Pathogenic 
      variants in mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) lead to defects in 
      OxPhos and physiological malfunctions (Nat Rev Dis Primer 2016;2:16080.). 
      Patients with primary mitochondrial disorders (PMD) experience heterogeneous 
      symptoms, typically in multiple organ systems, depending on the tissues affected 
      by mitochondrial dysfunction. Because of this heterogeneity, clinical diagnosis 
      is challenging (Annu Rev Genomics Hum Genet 2017;18:257-75.). Laboratory 
      diagnosis of mitochondrial disease depends on a multipronged analysis that can 
      include biochemical, histopathologic, and genetic testing. Each of these 
      modalities has complementary strengths and limitations in diagnostic utility. 
      CONTENT: The primary focus of this review is on diagnosis and testing strategies 
      for primary mitochondrial diseases. We review tissue samples utilized for 
      testing, metabolic signatures, histologic findings, and molecular testing 
      approaches. We conclude with future perspectives on mitochondrial testing. 
      SUMMARY: This review offers an overview of the current biochemical, histologic, 
      and genetic approaches available for mitochondrial testing. For each we review 
      their diagnostic utility including complementary strengths and weaknesses. We 
      identify gaps in current testing and possible future avenues for test 
      development.
CI  - (c) American Association for Clinical Chemistry 2023. All rights reserved. For 
      permissions, please e-mail: journals.permissions@oup.com.
FAU - Gill, Emily L
AU  - Gill EL
AUID- ORCID: 0000-0002-6562-3001
AD  - Department of Pathology and Laboratory Medicine, Children's Hospital of 
      Philadelphia, Philadelphia, PA, United States.
AD  - Department of Pathology and Laboratory Medicine, University of Pennsylvania, 
      Philadelphia, PA, United States.
FAU - Wang, Jing
AU  - Wang J
AD  - Department of Pathology and Laboratory Medicine, Children's Hospital of 
      Philadelphia, Philadelphia, PA, United States.
FAU - Viaene, Angela N
AU  - Viaene AN
AD  - Department of Pathology and Laboratory Medicine, Children's Hospital of 
      Philadelphia, Philadelphia, PA, United States.
AD  - Department of Pathology and Laboratory Medicine, University of Pennsylvania, 
      Philadelphia, PA, United States.
FAU - Master, Stephen R
AU  - Master SR
AUID- ORCID: 0000-0002-6808-631X
AD  - Department of Pathology and Laboratory Medicine, Children's Hospital of 
      Philadelphia, Philadelphia, PA, United States.
FAU - Ganetzky, Rebecca D
AU  - Ganetzky RD
AUID- ORCID: 0000-0001-6238-8109
AD  - Department of Pathology and Laboratory Medicine, Children's Hospital of 
      Philadelphia, Philadelphia, PA, United States.
AD  - Division of Human Genetics, Children's Hospital of Philadelphia, Mitochondrial 
      Medicine Frontier Program, Philadelphia, PA, United States.
AD  - Department of Pediatrics, University of Pennsylvania, Philadelphia, PA, United 
      States.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - England
TA  - Clin Chem
JT  - Clinical chemistry
JID - 9421549
RN  - 0 (DNA, Mitochondrial)
SB  - IM
MH  - Humans
MH  - Electron Transport
MH  - *Mitochondria/genetics
MH  - *Mitochondrial Diseases/diagnosis/genetics
MH  - DNA, Mitochondrial/genetics
MH  - Oxidative Phosphorylation
EDAT- 2023/04/26 18:42
MHDA- 2023/06/02 06:42
CRDT- 2023/04/26 14:42
PHST- 2022/08/01 00:00 [received]
PHST- 2023/03/03 00:00 [accepted]
PHST- 2023/06/02 06:42 [medline]
PHST- 2023/04/26 18:42 [pubmed]
PHST- 2023/04/26 14:42 [entrez]
AID - 7143230 [pii]
AID - 10.1093/clinchem/hvad037 [doi]
PST - ppublish
SO  - Clin Chem. 2023 Jun 1;69(6):564-582. doi: 10.1093/clinchem/hvad037.