Complex-I defect with minimal manifestations

Mitochondrial disorders (MIDs) present with a broad range of clinical manifestations [1] and often with large intra-and interfamilial pheno-typic heterogeneity [2], which is why it is often difficult to suspect an MID. In single cases or at onset of the disease, manifestations may be mild and non-specific [3], as in the following case. The patient is a 56-year-old Caucasian male, with a history of myal-gias of the external eye muscles during one month with onset in March 2011 after intake of fluvastatin between December 2010 and January 2011. Afterwards he experienced muscle aching of the thighs, which occasionally had a pulsatile character, with maximal intensity at the left adductor muscles. Since August 2011 he had also noted muscle wasting of the upper arm and thigh muscles. Myalgias were already present after awakening in the morning and generalized to all muscles. Additionally, he complained about easy fatigability, vertigo triggered by head movements , and exertional dyspnea. Years before, he had reacted with " chest pain " to simvastatin. He was working as a controller and described his job as stressful, due to which he had reduced his working hours to 20 h/ week. The family history was positive for hyperlipidemia (mother), arterial hypertension (mother), " rheumatological disease " (mother), renal insufficiency (mother), diabetes (grandmother from the mother's side), pancreatic carcinoma (grandmother from the mother's side), corpus carcinoma (sister), cerebral tumor (female cousin), and renal carcinoma (uncle). Clinical neurologic investigation revealed sore neck muscles, generally reduced tendon reflexes, incipient wasting of the left arm and the right thigh, and fasciculations on the right calve. Extensive work-up for neuromuscular disorders revealed leucopenia, cholesterol of 324 mg/ dl, triglycerides of 225 mg/dl, reduced folic acid, a positive western blot for myositis antibodies, reduced conduction velocity of the left perone-al nerve attributable to a previous postoperative defect, and a myogen-ic EMG of the right deltoid muscle. Creatine-kinase and serum lactate were normal whenever tested. Muscle biopsy of the left deltoid muscle revealed slightly increased fiber size variation and scattered COX-negative fibers. Despite this result, rheumatologists prescribed prednisolone (initially 25 mg/day, later tapered down to 6.25 mg) but without effect. Biochemical investigations of the muscle homogenate revealed markedly reduced activity of NADH-CoQ-oxido-reductase per gram of non-colla-gen protein as well as citrate synthase. Screening for mtDNA deletions, insertions, or depletion is under way. Echocardiography showed mild