Merck

Mitochondrial encephalomyopathy due to a novel mutation in ACAD9.

JAMA neurology (2013-07-10)
Caterina Garone, Maria Alice Donati, Michele Sacchini, Beatriz Garcia-Diaz, Claudio Bruno, Sarah Calvo, Vamsi K Mootha, Salvatore Dimauro
ABSTRACT

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. 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%). 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
(−)-Riboflavin, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥98%
Sigma-Aldrich
(−)-Riboflavin, from Eremothecium ashbyii, ≥98%
Sigma-Aldrich
(−)-Riboflavin, meets USP testing specifications
Supelco
Riboflavin, Pharmaceutical Secondary Standard; Certified Reference Material
Riboflavin, European Pharmacopoeia (EP) Reference Standard
Supelco
Riboflavin (B2), analytical standard