Diagnosis and Management of Kearns-Sayre Syndrome Rely on Comprehensive Clinical Evaluation

DNA studies in patients with Kearns‑Sayre syndrome and chronic progressive external ophthalmoplegia. We appreciate the readers' interest and their comprehensive comments and advice about the article, [1] which mainly concerned details of the patients' information. In this paper, we reported 19 Kearns‑Sayre syndrome (KSS) patients whose diagnoses were in accordance with the current clinical diagnostic criteria of KSS, i.e., the triad of progressive external ophthalmoplegia, pigmentary retinopathy, and onset before 20 years of age, plus at least one of the followings: heart block, cerebellar symptoms, or cerebrospinal fluid protein levels above 1000 mg/L. The diagnostic criteria have been widely used. Apart from clinical features, muscle pathology and molecular genetic analysis can play a great role in the diagnostic workup. Muscle pathology showed ragged‑red fibers (RRF), ragged‑blue fibers (RBF), or cytochrome c‑oxidase (COX)‑negative fibers in almost all patients. Southern blot or long‑range polymerase chain reaction can detect single large‑scale deletion in about 90% of KSS patients, [5] while mitochondrial DNA (mtDNA) point mutations or nuclear gene mutations have been reported in other KSS patients. [6] In general, single large‑scale deletion can be detected only from the muscle, but not from blood cells of KSS patients. Among the 19 patients reported by us, 15 patients underwent muscle biopsy in our hospital which showed RRF, RBF, and COX‑negative fibers in all of them; however, mtDNA mutation detection was available in 11 of them because muscle tissue of the other four (patients 8, 10, 17, and 18) were not enough for further gene analyses; one patient (patient 12) had muscle biopsy in another hospital, and we got a little muscle tissue to do the mutation examination although RBF% cannot be counted. Three patients (patients 2, 5, and 7) refused to receive muscle biopsy, but all of them showed typical KSS features. We performed common mtDNA point mutations analysis (mtDNA A3243G, A8344G) in their blood, which were negative. Biochemical investigations, especially activity assay of respiratory chain complexes in muscle tissues, can also help provide evidence for the diagnosis of mitochondrial disease. Unfortunately, such a detecting platform has not been established in our laboratory. There were several articles studying the exact nature of high signal lesions on diffusion‑weighted imaging (DWI) in patients with mitochondrial diseases, especially mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke‑like episodes. However, the results were conflicting since some reported an increase in the apparent diffusion coefficient (ADC) values suggesting vasogenic edema while others …