**5. Leigh syndrome**

Leigh syndrome also defined as "subacute necrotizing encephalomyelopathy" is characterized by focal, bilateral, and symmetric necrotic lesions associated with demyelination, vascular proliferation, and gliosis in the brain stem, diencephalon, basal ganglia, cerebellum, and (occasionally) cerebral white matter.

The syndrome has early onset with hypotonia, failure to thrive, psychomotor regression, and brain stem and basal ganglia dysfunction with ataxia, ocular movement abnormalities, dystonia, and swallowing and respiratory disturbances. It can be inherited as autosomal recessive trait or as autosomal dominant or X-linked mechanism, while other patients show maternal inheritance (MILS). It can be associated with functional or molecular defects in several enzyme systems (pyruvate dehydrogenase complex: PDHC), respiratory chain complexes I–IV (cytochrome c oxidase: COX), and mitochondria-encoded ATPase 6 subunit of complex V.

involved in controlling the nuclear-mitochondrial intergenomic signaling (Spinazzola and

Developmental delay or dementia, lactic acidosis, cyclic vomiting, seizures, failure to thrive, hearing loss, myopathy, liver failure, renal tubular acidosis, pancreatitis, manifesting at 1-3

*Myoclonic epilepsy, myopathy, sensory ataxia (MEMSA)* is characterized by epilepsy, myopathy, ataxia without ophthalmoplegia (previously defined as spinocerebellar ataxia

Ataxia neuropathy spectrum (ANS) is characterized by ataxia and neuropathy, seizures (reported in two-thirds of the patients), ophthalmoplegia (one-half), clinical myopathy (rare). This disorder was previously defined as recessive ataxia syndrome: MIRAS and

Autosomal Recessive progressive external ophthalmoplegia (arPEO) and Autosomal Dominant progressive external ophthalmoplegia (adPEO) are characterized by myopathy, variable sensorineural hearing loss, axonal neuropathy, ataxia, depression, parkinsonism, hypogonadism, and cataracts (previously defined as CPEO plus). Seizures are uncommon; however, few patients may have signs reminding those observed in MELAS syndrome, including stroke-like episodes and seizures (Deschauer et al, 2007). These syndromes are typically associated with mutations in the nuclear-encoded DNA polymerase-gamma gene

The syndrome variably defined as Alpers' disease, Alpers' syndrome, Alpers-Huttenlocher's disease, progressive neuronal degeneration of childhood, progressive sclerosing poliodystrophy or progressive infantile poliodystrophy is characterized by neuronal degeneration of the cerebral cortex and elsewhere, caused by recessive mutations in nDNA, coding for the mitochondrial DNA polymerase-gamma. In this syndrome, the onset is usually before age four years and up to age 25-35; often there is pre-existing developmental delays of variable severity. The syndrome is characterized by seizures, episodic psychomotor regression, liver dysfunction or failure, which may follow exposure to certain antiepileptic medication. The electro-clinical pattern is typically characterized by periodic

Leigh syndrome also defined as "subacute necrotizing encephalomyelopathy" is characterized by focal, bilateral, and symmetric necrotic lesions associated with demyelination, vascular proliferation, and gliosis in the brain stem, diencephalon, basal

The syndrome has early onset with hypotonia, failure to thrive, psychomotor regression, and brain stem and basal ganglia dysfunction with ataxia, ocular movement abnormalities, dystonia, and swallowing and respiratory disturbances. It can be inherited as autosomal recessive trait or as autosomal dominant or X-linked mechanism, while other patients show maternal inheritance (MILS). It can be associated with functional or molecular defects in several enzyme systems (pyruvate dehydrogenase complex: PDHC), respiratory chain complexes I–IV (cytochrome c oxidase: COX), and mitochondria-encoded ATPase 6 subunit

months, characterize childhood myo-cerebro-hepatopathy spectrum (MCHS).

sensory ataxia neuropathy dysarthria and ophthalmoplegia: SANDO.

Zeviani, 2005).

with epilepsy: SCAE).

(gene map locus: 15q25).

**5. Leigh syndrome** 

of complex V.

EEG and epilepsia partialis continua.

ganglia, cerebellum, and (occasionally) cerebral white matter.

These conditions include the following syndromes:

Molecular exams could identify heterogeneous mutations in various mitochondrial and nuclear genes coding for complex I, complex III and complex IV and complex V gene. Mutations have been found also in genes encoding mitochondrial tRNA proteins (MTTV, MTTK, MTTW, and MTTL1) and in components of the pyruvate dehydrogenase complex (e.g. PDHA1: X-linked Leigh syndrome). The French-Canadian (or Saguenay-Lac Saint Jean) type of Leigh syndrome with COX deficiency (LSFC) is caused by mutation in the LRPPRC gene. Deficiency of coenzyme Q10 can present as Leigh syndrome.

In the Leigh syndrome, both generalized and focal seizures have been described, according to genetic and biochemical heterogeneity.
