Background
Leigh syndrome (LS) is a rare and inherited heterogeneous disease which is associated with progressive neurodegenerative brain damage. Diarrhea, vomiting and dysphagia are usually the initial signs of Leigh syndrome in infants. Clinically, it may be also associated with multiple features, including brainstem symptoms, ataxia, hypotonia, dystonia, respiratory insufficiency, pyramidal signs, lactic acidosis in blood or cerebrospinal fluid and hypertrophic cardiomyopathy (1). It is usually associated with cerebral hypotonia, movement and mental disabilities and respiratory failure which results in death within 2-3 years (2). Weakness of limbs and loss of sensation are also common in these cases (3). Although the basic neuropathological features in affected children are relatively similar, there is heterogeneity in clinical, genetic and biochemistry findings. Therefore, early diagnosis of the disease is essential to increase survival in affected patients.
The molecular mechanism underlying LS pathogenesis is mainly due to the defects in mitochondrial respiratory chain enzymes (4). Recent evidences have revealed that mutations in genes for the pyruvate dehydrogenase complex, ATP synthase subunit-6, cytochrome-c oxidase, and subunits of mitochondrial complex-I are responsible for LS (4, 5). NADH: ubiquinone oxidoreductase, encoded by NDUFS4 gene, is a subunit of mitochondrial complex-I which catalyzes the oxidation of NADH (6).NDUFS4 gene is located in 5q11.2, which spans of eight exons. This gene encodes a nuclear-encoded accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (complex I, or NADH: ubiquinone oxidoreductase). Complex I removes electrons from NADH and passes them to the electron acceptor ubiquinone. Mutations in this gene can cause mitochondrial complex I deficiencies such as Leigh syndrome. More than 35 different genes have been identified in the mitochondrial respiratory chain that is associated with Leigh syndrome. Nearly 25% of Leigh disease mutations detected in the mitochondrial genome. Here, this is the first case of LS from Iran with NDFUS4gene mutation presented with horizontal gaze palsy.