Journal
JAMA NEUROLOGY
Volume 70, Issue 9, Pages 1177-1179Publisher
AMER MEDICAL ASSOC
DOI: 10.1001/jamaneurol.2013.3197
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Funding
- National Institutes of Health [HD032062]
- Italian Congenital Metabolic Disorders Association
- Marriott Mitochondrial Disorders Clinical Research Fund
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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 ofWestern 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.
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