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.