LEIGH4S SYNDROME AND IT'S PHENOTYPIC VARIABILITY IN THE ADULT METABOLIC POPULATION Massano A 1 , Teotónio R 1 , Silva F 1 , Isidoro L 1 , Domingues J 1 , Garcia P 2 , Diogo L 2 , Grazina M 3 , Macário MC 1 1 Adult Neurology Department-HUC, Coimbra, Portugal 2 Metabolic Disease Unit-Pediatric Hosp, Coimbra, Portugal 3 Centro Neurociências de Coimbra, Coimbra, Portugal Leigh's syndrome is a mitochondrial disease related to various enzymatic defects that affect the oxidative metabolism and may occur in atypical way. Cases: 1: 34 years old male begins ataxia, gait impairment and frequent falls at 3 years old. Later develops uncontrollable vomiting, ophthalmoplegia, hemiparesis and right hemidystonia. Laboratory tests show mutation of the gene SURF1. 2: Male, 22 years old, with depressed mood at the age of 10 and behavioral changes associated with auditory-verbal hallucinations at 19 years old. 3: 22 years old lady, with hypertrophic cardiomyopathy diagnosed at 3 years old. She started loss of coordination, at 8 years, progressing to a lower limb dystonia, involuntary choreo-dystonic movements and cognitive deterioration with increasing learning disability. 4: Female who started at the age of 13, after a flu syndrome, a "Guillain-Barré syndrome like" with generalized hypotonia, distal tetraparesis and a bilateral hypoesthesia in glove and half. She died at 20 years old after development of neurologic deteriorations. All this 4 patients have lactic acidosis and typical Brain MRI. We bring 4 patients with Leigh's syndrome, who have distinct age or mode of presentation and clinical course. We intended to enhance the great phenotypic variability of this neurometabolic disease. Mitochondrial respiratory chain disorders (MRC), defined as primary diseases of the oxidative phosphorylation system are difficult to diagnose and classify. The aim is to characterize primary findings on histopathology of muscle biopsies performed in patients with definitive MRC. The study included patients of our neurometabolic adult consultation that fulfilled Walker's criteria for definitive MRC and had had a muscle biopsy performed. A total of 48 patients were assigned. 37.5% of the biopsies were considered normal. In the group with clinically predominant muscle involvement (group 1), the biopsy showed changes consistent with mitochondrial disease in 82% of cases against 37,5% on the other patients (group 2). COX-negative fibres were found in 64% of group 1 and 37,5% of group 2. In the first group, "red-ragged fibres" were seen in 71,4%, but only in sufficient number to be considered pathologic in 46,4%, while in the second group these numbers decreased to 50 and 25% respectively. Some other minor changes were seen: atrophy, blue-ragged fibres and increase in the variability of fibres diameter. Muscle biopsy is an important study in MRC disorders, and there appears to be good correlation between changes in it and a diagnosis of MRC with predominant involvement of muscle.