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JAMA Neurol. 2013 Sep 1;70(9):1177-9. doi: 10.1001/jamaneurol.2013.3197.

Mitochondrial encephalomyopathy due to a novel mutation in ACAD9.

Author information

1
Department of Neurology, Columbia University Medical Center, College of Physicians and Surgeons, New York, New York2Human Genetics, Joint PhD Program, Universities of Turin and Bologna, Italy.

Abstract

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.

PMID:
23836383
PMCID:
PMC3891824
DOI:
10.1001/jamaneurol.2013.3197
[Indexed for MEDLINE]
Free PMC Article
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