title: Non-invasive evaluation of buccal respiratory chain enzyme dysfunction in mitochondrial disease: comparison with studies in muscle biopsy.
abstract: Making a diagnosis of mitochondrial disease (MD) is extremely challenging and often employs the analysis of respiratory complex (RC) activities in biopsied skeletal muscle. Given both the invasive nature and expense of biopsied-muscle based testing for mitochondrial defects, buccal swab enzyme analysis has been explored as an alternative approach to the more invasive muscle biopsy. Case studies have recently suggested that buccal swabs from patients can be used to accurately assess mitochondrial enzyme activities including RC I and RC IV using a dipstick methodology combined with spectrophotometric analysis. In this study, forty patients with suspected MD who have previously been found to have significant defects in either RC I or RC IV in skeletal muscle were assessed by buccal swab analysis and compared to enzyme values obtained with unaffected controls (n=106) in the same age range. Buccal citrate synthase was used as an indicator of overall mitochondrial content, correlating well with overall buccal mitochondrial frataxin levels and was found to be elevated above control levels in 28% of the patients in this cohort. Of 26 cases with significant muscle RC I deficiency, 20 displayed significantly reduced levels of buccal RC I activity. All 7 of the patients with muscle RC IV deficiency showed significant buccal RC IV defect and 6 of the 7 patients with combined defects in muscle RC I and IV activity levels also exhibited analogous deficiencies in both buccal RC I and RC IV activities. In conclusion, the relatively high correlation (over 82%) of buccal and muscle RC deficiencies further supports the validity of this non-invasive approach as a potentially useful tool in the diagnosis of MD.
authors.affiliation: Section of Neurology, Department of Pediatrics, St. Christopher's Hospital for Children, Drexel University College of Medicine, Philadelphia, PA 19134, USA. michael.goldenthal@drexelmed.edu
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Goldenthal
authors.forename: Teddy
authors.initials: T
authors.lastname: Kuruvilla
authors.forename: Shirish
authors.initials: S
authors.lastname: Damle
authors.forename: Leon
authors.initials: L
authors.lastname: Salganicoff
authors.forename: Sudip
authors.initials: S
authors.lastname: Sheth
authors.forename: Nidhi
authors.initials: N
authors.lastname: Shah
authors.forename: Harold
authors.initials: H
authors.lastname: Marks
authors.forename: Divya
authors.initials: D
authors.lastname: Khurana
authors.forename: Ignacio
authors.initials: I
authors.lastname: Valencia
authors.forename: Agustin
authors.initials: A
authors.lastname: Legido
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002950:Citrate (si)-Synthase / Q000378:metabolism*; D015331:Cohort Studies; D004272:DNA, Mitochondrial / Q000378:metabolism; D004579:Electron Transport; D042967:Electron Transport Complex I / Q000378:metabolism; D005260:Female; D006801:Humans; D033862:Iron-Binding Proteins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism; D008931:Mitochondria, Muscle / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000175:diagnosis* / Q000201:enzymology* / Q000378:metabolism; D009061:Mouth Mucosa / Q000201:enzymology*; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism; D010085:Oxidative Phosphorylation; D055815:Young Adult; D000096923:Frataxin
chemical_list: D002950:Citrate (si)-Synthase; D004272:DNA, Mitochondrial; D042967:Electron Transport Complex I; D033862:Iron-Binding Proteins; D000096923:Frataxin