We're unable to sign you in at this time. Please try again in a few minutes.
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Editorial |

Mitochondrial Extrapyramidal Syndromes Using Age and Phenomenology to Guide Genetic Testing

Robert D. S. Pitceathly, MD, PhD1,2
[+] Author Affiliations
1MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, England
2Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, England
JAMA Neurol. 2016;73(6):630-632. doi:10.1001/jamaneurol.2016.0756.
Text Size: A A A
Published online


Mitochondrial disorders pose a major diagnostic challenge to clinicians given their significant phenotypic and genetic diversity. This dilemma is underpinned by the dual genomic expression of mitochondrial proteins, which are encoded by both nuclear and mitochondrial genetic material. Mitochondrial DNA (mtDNA)–related disease is further complicated by polyploidy, with hundreds to thousands of mtDNA molecules per cell. Consequently, patients with mtDNA mutations frequently harbor 2 discrete mtDNA populations (so-called mutant and wild type) at variable ratios, a biological phenomenon termed heteroplasmy. The proportion of mutant to wild-type mtDNA and tissue distribution often varies considerably among patients harboring identical mtDNA mutations. Furthermore, the biochemical threshold necessary for a disease to manifest can fluctuate depending on the mtDNA mutation and the energy requirements of the target organ. For instance, skeletal muscle, brain, heart, and neural tissue are all critically dependent on adenosine triphosphate produced by mitochondria and therefore have a low threshold to cellular bioenergetic failure as a consequence of mitochondrial dysfunction. Overall, these factors, in addition to numerous environmental and epigenetic modulators, coalesce to determine the severity and phenotypic spectrum of the disease.

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

First Page Preview

View Large
First page PDF preview





Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.


Some tools below are only available to our subscribers or users with an online account.

0 Citations

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.

See Also...
Articles Related By Topic
Related Collections

The Rational Clinical Examination: Evidence-Based Clinical Diagnosis

The Rational Clinical Examination: Evidence-Based Clinical Diagnosis
Make the Diagnosis: Parkinsonism