0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
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 ......
Case Report/Case Series |

Mitochondrial Encephalomyopathy Due to a Novel Mutation in ACAD9

Caterina Garone, MD1,2; Maria Alice Donati, MD3; Michele Sacchini, MD3; Beatriz Garcia-Diaz, PhD1; Claudio Bruno, MD4; Sarah Calvo, PhD5,6,7; Vamsi K. Mootha, MD5,6,7; Salvatore DiMauro, MD1
[+] Author Affiliations
1Department of Neurology, Columbia University Medical Center, College of Physicians and Surgeons, New York, New York
2Human Genetics, Joint PhD Program, Universities of Turin and Bologna, Italy
3Metabolic and Muscular Unit, Department of Pediatrics, University of Florence, Meyer Children's Hospital, Italy
4Unit of Muscular and Neurodegenerative Disease, IRCCS G. Gaslini Institute, Genova, Italy
5Department of Molecular Biology, Massachusetts General Hospital, Boston
6Department of Systems Biology, Harvard Medical School, Boston, Massachusetts
7Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge, Massachusetts
JAMA Neurol. 2013;70(9):1177-1179. doi:10.1001/jamaneurol.2013.3197.
Text Size: A A A
Published online

Importance  Mendelian forms of complex I deficiency are usually associated with fatal infantile encephalomyopathy. Application of “MitoExome” sequencing (deep sequencing of the entire mitochondrial genome and the coding exons of >1000 nuclear genes encoding the mitochondrial proteome) allowed us to reveal an unusual clinical variant of complex I deficiency due to a novel homozygous mutation in ACAD9. The patient had an infantile-onset but slowly progressive encephalomyopathy and responded favorably to riboflavin therapy.

Observation  A 13-year-old boy had exercise intolerance, weakness, and mild psychomotor delay. Muscle histochemistry showed mitochondrial proliferation, and biochemical analysis revealed severe complex I deficiency (15% of normal). The level of complex I holoprotein was reduced as determined by use of Western blot both in muscle (54%) and in fibroblasts (57%).

Conclusions and Relevance  The clinical presentation of complex I deficiency due ACAD9 mutations spans from fatal infantile encephalocardiomyopathy to mild encephalomyopathy. Our data support the notion that ACAD9 functions as a complex I assembly protein. ACAD9 is a flavin adenine dinucleotide–containing flavoprotein, and treatment with riboflavin is advisable.

Figures in this Article

Sign in

Create a free personal account to sign up for alerts, share articles, and more.

Purchase Options

• Buy this article
• Subscribe to the journal

Figures

Place holder to copy figure label and caption
Figure.
Clinical, Histochemical, Biochemical, and Molecular Genetic Characteristics of the Patient

The patient at 13 years of age shows scoliosis and truncal obesity (A); Gomori trichrome (B [original magnification ×20]) and cytochrome c oxidase (C [original magnification ×20]) histochemical stains show mitochondrial proliferation. Images of Western blot analysis of oxidative phosphorylation proteins (D) in the fibroblasts (left) and muscle (right) of the patient (P) and controls (C) are shown. I indicates complex; II, complex II; III, complex III; IV, complex IV; and V, complex V. The electropherogram of the patient’s DNA shows the variant (c.1240C>T) and evolutionary conservation of the mutated amino acid (E).

Graphic Jump Location

Tables

References

Correspondence

CME
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.
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.
Submit a Comment

Multimedia

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

Web of Science® Times Cited: 2

Sign in

Create a free personal account to sign up for alerts, share articles, and more.

Purchase Options

• Buy this article
• Subscribe to the journal

Related Content

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

Articles Related By Topic
Related Collections
PubMed Articles
Jobs
brightcove.createExperiences();