LAUSR

The sporadic occurrence of a mitochondrial disease, including chronic progressive external ophthalmoplegia (CPEO), Kearns–Sayre syndrome (KSS, MIM 530000), and in infancy, Pearson syndrome (MIM 557000) may suggest the presence of a single, sporadic mitochondrial DNA (mtDNA) deletion associated with typical ‘‘mitochondrial’’ features in skeletal muscle biopsies [1]. In particular, about 90% of individuals with KSS have a large-scale (more than 1 kb) mtDNA deletion that is usually present in all tissues, but predominantly in muscle. In Pearson syndrome, mtDNA deletions are usually more abundant in blood than in other tissues, whereas in PEO, the deletions are confined to skeletal muscle. Contrary to multiple mtDNA deletions, due to defect of mtDNA maintenance, single deletions occur mainly in regions flanked by short repeated sequences, and can develop during repair of damaged mtDNA [2]. No correlation exists between size or location of the mtDNA deletion and phenotype. Patients with mitochondrial myopathy may develop additional neurological features; also peripheral neuropathy is a frequent manifestation of mitochondrial disease [3]. In particular, it is highly predictive of an underlying nuclear DNA defect and it has been reported in about 6% of patients with single deletions of mtDNA [4, 5]. Interestingly, the occurrence of atypical CPEO with single mtDNA deletion and motor neuron disease (MND) has been reported only once [6]. We describe a patient with CPEO and signs of denervating disease involvement carrying a novel single largescale mtDNA deletion. This case may expand the clinical and histological spectrum of mitochondrial diseases. A 45-year-old man with a family history negative for neuromuscular disorders presented progressive diplopia with onset in his 30 s. Since last year, the patient referred fatigability, difficulty in rising from the chair and climbing stairs. Neurological examination showed ptosis, ophthalmoplegia, weakness of pharyngeal reflex and slight proximal muscle weakness. His clinical history was completely negative for signs of sensitive impairment or for neuropathic pain. Further clinical evaluation of the deep and superficial sensitivity pathway and tendon reflexes was normal. There were no signs of fasciculation, cerebellar, pyramidal/extrapyramidal or cognitive impairment. Electromyography (EMG) was consistent with widespread neurogenic changes, including spontaneous fibrillations, positive sharp waves and complex repetitive discharges in the biceps brachii, triceps brachii, rectus femoris and tibialis anterior, bilaterally while the duration of action potentials was normal. Nerve conduction studies still showed normal value for velocity and amplitude of potential. Moreover, cerebral and cervical spine MRI was normal. The clinical and EMG follow-up 3 years later showed an unchanged picture. A muscle biopsy of left biceps brachii, performed at age 44, revealed a group of atrophic & Lucia Ruggiero [email protected]