Study Investigates Simple Diagnosis for Cytochrome c Oxidase Deficiency

Children with mitochondrial disorders most commonly are deficient in cytochrome c oxidase (CIV), a protein involved in the electron transport chain the membrane of the mitochondria. The gold standard way of diagnosing CIV deficiency is taking a muscle biopsy and conducting a biochemical analysis on the tissue. Small children experience a great deal of stress during the procedure, prompting the necessity to develop a less-invasive means of CIV deficiency diagnosis.

In the laboratory of Dr. H. Hansikova at Charles University and General University Hospital in Prague, a group of researchers studied the use of dipstick immunocapture assay (DIA) to measure the amount of CIV present in patients. Cells for the DIA were obtained through a simple buccal smear, where the inside of the cheek was swabbed to obtain cells.

“It would be highly advantageous if some of the needed biochemical analyses could be performed with tissues obtained using non-invasive methods,” wrote lead author Dr. M. Rodinova. “The aims of our study were to minimize the patient burden and to test the efficacy of DIA for the diagnosis of CIV deficiency in non-invasively obtained buccal epithelial cells.”

A small set of patients was studied in the article, “Non-Invasive Screening of Cytochrome c Oxidase Deficiency in Children Using a Dipstick Immunocapture Assay,” which was published in Folia Biologica. Five patients with Leigh syndrome, the most common mitochondrial myopathy, were evaluated with the DIA. Three of the patients had known CIV deficiency, previously confirmed via muscle biopsy, and two of the patients had suspected CIV. After a few buccal swabs were obtained, the researchers used two DIA kits to measure CIV expression in buccal epithelial cells and fibroblasts previously taken from patients’ skin.

Results from the DIA showed a lower level of CIV in confirmed deficient patients and suspected deficient patients than in control individuals without a deficiency. The activity of CIV in fibroblasts was also lower in CIV-deficient patients.

“The diagnosis of mitochondrial disorders is difficult in many patients due to overlapping symptoms and tissue-specific changes that often result in the need for invasive procedures, including muscle biopsies,” wrote Dr. Rodinova. “The dipstick immunocapture assay (DIA) is a simple, rapid and sensitive method for non-invasive screening and diagnosis in patients with mitochondrial disorders resulting from CIV deficiency.”