The phenotypic spectrum of fifty Czech m.3243A> G carriers

Abstract Background Mitochondrial myopathy, Encephalopathy, Lactic Acidosis and Stroke-like episodes syndrome (MELAS) is a common mitochondrial disorder with varying multisystemic clinical manifestation. We present a comprehensive clinical picture of 50 Czech m.3243A> G carriers with emphasis on the sequence of symptoms in symptomatic patients. Results Symptoms developed in 33 patients (66%) and 17 carriers remained unaffected (34%). The age of onset varied from 1 month to 47 years of age, with juvenile presentation occurring in 53% of patients. Myopathy was the most common presenting symptom (18%), followed by CPEO/ptosis and hearing loss, with the latter also being the most common second symptom. Stroke-like episodes (SLE) occurred in fourteen patients, although never as a first symptom, and were frequently preceded by migraines (58%). Rhabdomyolysis developed in two patients. The second symptom appeared 5.0 ± 8.3 years (range 0–28 years) after the first, and the interval between the second and third symptom was 2.0 ± 6.0 years (range 0–21 years). Four of our patients remained monosymptomatic up to 12 years of follow-up. The sequence of symptoms according to their time of manifestation was migraines, myopathy, seizures, CPEO/ptosis, SLE, hearing loss, and diabetes mellitus. The average age at death was 32.4 ± 17.7 years (range 9–60 years) in the juvenile form and 44.0 ± 12.7 years (range 35–53 years) in the adult form. Some patients with SLE harboured very low heteroplasmy levels in various tissues. No threshold for any organ dysfunction could be determined based on these levels. Conclusions Sufficient knowledge of the timeline of the natural course of MELAS syndrome may improve the prediction and management of symptoms in patients with this mitochondrial disease.