MELAS syndrome in a patient with a point mutation in MTTS1 Introduction Mitochondrial tRNA mutations are a frequent cause of complex neurological syndromes. Distinct clinical entities, such as myoclonus epilepsy with ragged red fibres (MERRF) and mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) are caused by mt tRNA Lys (MTTK) (1, 2) and mt tRNA Leu(UUR) (MTTL1) (3) mutations. In contrast, mutations in the tRNA Ser(UCN) gene (MTTS1) are found in patients with a spectrum of clinical presentations. Patients with a combination of hearing loss, myoclonus epilepsy, tonic–clonic seizures and cognitive decline were found to have the 7472insC mutation (4,5), hearing loss, mental retardation and ataxia (7472insC mutation and A7472C polymorphism) (6), a combination of sensorineural hearing loss, myoclonus and ataxia (7, 8), progressive myopathy and ragged red fibres (G7497A) (5), monomelic amyotrophy and hearing loss (7472insC) (9). Non- syndromic hearing loss has been described in several families (T7511C) (10–15). In addition, patients with only muscular symptoms such as exercise intolerance (8) and late-onset myopathy (16) have been reported. Clinical descriptions of patients from three families, who have previously been reported to harbour the T7512C mutation appear in Table 1 (5, 17). We describe a patient with MELAS syndrome harbouring a mutation in the tRNA Ser(UCN) gene showing heteroplasmy in blood, muscle and hair shafts. Patient and methods Patient The patient is a woman aged 44 years. Her mother and sister are healthy. At the age of 4 years, she presented with epilepsy. Data on the clinical phenotype of the epilepsy or EEG recordings are unavailable. From the age of 19 to 35 years, she was free from epileptic attacks and medication Acta Neurol Scand 2008: 117: 128–132 DOI: 10.1111/j.1600-0404.2007.00913.x Copyright Ó 2007 The Authors Journal compilation Ó 2007 Blackwell Munksgaard ACTA NEUROLOGICA SCANDINAVICA Lindberg C, Moslemi A-R, Oldfors A. MELAS syndrome in a patient with a point mutation in MTTS1. Acta Neurol Scand 2008: 117: 128–132. Ó 2007 The Authors Journal compilation Ó 2007 Blackwell Munksgaard. Background, Objective and Methods – We describe a female patient with a mitochondrial encephalopathy, lactic acidosis and stroke-like episodes syndrome. As a child, she developed epilepsy and stroke-like episodes giving cognitive impairment and ataxia but no hearing impairment. At the age of 44 years, she suffered a cerebral sinus thrombosis which was warfarin treated. One month later, she developed an episode of severe acidosis associated with encephalopathy and myelopathy. Results – She was found to harbour a 7512T>C mutation in the mitochondrial encoded tRNA Ser(UCN) gene (MTTS1). The mutation load was 91% in muscle and 24% in blood. Enzyme histochemical analysis of the muscle tissue showed numerous cytochrome c oxidase (COX)-negative fibres. Restriction fragment length polymorphism (RFLP) analysis of single muscle fibres showed significantly higher level (median 97%, range: 94–99%) of the mutation in the COX-negative fibres compared with COX-positive fibres (median 36%, range: 12–91%), demonstrating the pathogenic effect of the mutation. Different levels of heteroplasmy (range 34–61%) were detected in hair shafts analysed by RFLP. Conclusion – This case adds to the spectrum of clinical presentations, i.e. sinus thrombosis, in patients having MTTS1 mutations. C. Lindberg 1 , A.-R. Moslemi 2 , A. Oldfors 2 1 Department of Neurology, Neuromuscular Center, Sahlgrenska University Hospital, Gçteborg, Sweden; 2 Department of Pathology, Sahlgrenska University Hospital, Gçteborg, Sweden Key words: MELAS; mitochondrial tRNA; mutation; myelopathy; cerebral sinus thrombosis Christopher Lindberg, Department of Neurology, Neuromuscular Center, Sahlgrenska University Hospital, S-431 80 Mçlndal, Sweden Tel.: +46 31 3432100 Fax: +46 31 3431301 e-mail: christopher.lindberg@vgregion.se Accepted for publication July 2, 2007 128