Cytochromec oxidase deficiency in three patients with Leigh's disease

Abstract

Sabacute necrotizing encephalomyopathy, first reported by Leigh more than 30 years ago, is an autosomal recessive disorder characterized by multiple symmetrical loci of incomplete necrosis (spongy degeneration) in brainstem, spinal cord, basal ganglia and cerebellum. The clinical picture is heterogeneous, depending on the variability of lesions, but usually it consists of disorders of respiratory rhythm, nuclear and supranuclear oculomotor paralysis, other signs of cranial nerve dysfunction, abnormal movements, ataxia and optic atrophy.Different biochemical causes have been proposed: defects of pyruvate carboxylase, pyruvate dehydrogenase complex and the respiratory chain are reported in patients affected with Leigh's disease. We report here three new patients, in whose fibroblasts we found partial defects of cytochrome oxidase. We emphasize that the association of typical neuroradiological lesions with one of the proposed biochemical markers can lead to premortem diagnosis in living patients and to early genetic counselling. CASE REPORTCase 1: R. Cosimo is the first child of healthy, related parents (first cousins). He had normal psychomotor development during the first 2 years of age; after which time he began to show failure to thrive, vomiting, arm and head tremor and jerky eye movements. At the age of 3 years he was first admitted to our department. Clinical examination revealed hypotonia, paralysis of vertical gaze, horizontal nystagmus, cerebellar intentional tremor, inco-ordination and hyporeflexia; mental abilities were quite normal.Lactic acidaemia ranged between 40 and 30.3 mg dL -1 (normal values 5-20) and pyruvic acidaemia between 0.56 and 0.38 mg dL -1 (normal values 0.36--0.59). CSF proteins were 43 mg dL -a with normal electrophoretic pattern. The boy continued to deteriorate and at the age of 4 years he was readmitted to hospital. At this time the clinical picture consisted of cerebellar ataxia, optic atrophy and mental deterioration; nerve conduction velocity was decreased. CT scan showed typical basal ganglia lesions (Figure 1). The child is still alive at the age of 6 years and 189 Journal of Inherited Metabolic Disease. ISSN 0141-8955.