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Overview

What is Leigh Syndrome?

Denis Leigh first described this condition in 1951 and named it Subacute Necrotizing Encephalomyelopathy (SNE). He pronounced his name ‘Lee’ instead of ‘Lay’ [1].

Leigh syndrome (Leigh’s disease/syndrome) (LS) is a rare inherited neurodegenerative condition that affects the central nervous system and can be caused by mutations in mitochondrial DNA or nuclear DNA [2].  At least 1 in 40,000 newborns is affected by Leigh syndrome [3].

Leigh syndrome most often occurs in infants before 2 year of age, but late-onset Leigh syndrome, although rare, has also been reported in teenagers and adults [3]. The course of Leigh syndrome can be acute, subacute, episodic, or chronically progressive. In general, the later the onset, the slower the progression [2].

Signs and Symptoms

Frequent signs in neonatal and infantile onset:

Respiratory problems (irregular respiration, apnea, sighing, and hyperventilation)
Ocular abnormalities (strabismus, bizarre eye movements, external ophtahlmoplegia, ptosis, optic atrophy, nystagmus, loss of vision, impaired papillary reaction, retinal pigmentary degeneration)
Hypotonia
Pyramidal signs (spastic paresis, hyperreflexia, extensor plantar reflexes)
Weakness
Easy fatigability
Feeding problems (anorexia, difficulty in swallowing or sucking, vomiting, weight loss, and retarded growth)

Less frequent signs in neonatal and infantile onset:

Episodes of lethargy
Seizures
Deafness
Renal tubular dysfunction
Cardiac problems (cardiaomyopathy and disturbances of cardiac rhythm with periods of tachycardia and bradycardia)

Signs in later-onset:

Mental and motor retardation or deterioration
Exercise intolerance
Cerebellar signs (ataxia, dysarthria)
Extrapyramidal signs (rigidity, hyppokinesia, chorea, athetosis, myoclonus, tremor, ballismus)

Signs in acute onset:

Coma and convulsions
Sometimes status epilepticus

Inheritance of Leigh Syndrome

Leigh Syndrome can be generally classified into three categories: Mitochondrial-DNA Associated (Maternally-inherited), Autosomal Recessive, and X-linked. However, genetic components are NOT identified in some cases.

Mitochondrial-DNA Associated Leigh Syndrome
Mitochondrial-DNA Associated Leigh Syndrome is caused by a mutation in the mitochondrial DNA (mtDNA). Since mitochondria are passed from a mother to her children, this type of LS is also known as Maternally-inherited Leigh Syndrome.   Mitochondrion is the power house of the cell, so mutations in the mitochondrial DNA can cause a power shortage. When brain cells are deprived with energy, both the nervous system and the related motor movements are affected [2].

X-linked Leigh Syndrome
In X-linked Leigh Syndrome, mutations are found in PDHA1 gene, which is situated on the X chromosome. The product of this gene is a component of an enzyme, pyruvate dehydrogenase complex, which is responsible for providing fuel to mitochondria [4].

Autosomal Recessive Leigh Syndrome
What is autosomal recessive? (If you are interested in learning more about this term, please click on the term.)
Defects in different mitochondrial components can be responsible for this type of LS, and some of the corresponding genes locate in nuclear DNA. Cells with reduced mitochondrial function are energy-deprived and are not industrious cells. These cells would lead to problems in nervous system and motor functions [2].

Leigh-Like Syndrome

Patients with Leigh-like syndrome have atypical neurologic or radiologic features that suggest the presence of Leigh syndrome. In these patients, brainstem associated respiratory impairment is usually absent, and few or no abnormalities of ocular motility present. However, late-onset myopathy is described. Some patients may have seizures (infantile spasms or hypsarrhythmia), behavioural changes, hypotonia, dystonia, neuropathy, or retinopathy [3].

 

Reference

1. OMIM Entry – #256000 – LEIGH SYNDROME; LS .
2. van der Knapp, Marjo S and Valk, Jaap. Leigh Syndrome and Mitochondrial leukoencephalopathies. Magnetic Resonance of Myelination and Myelin Disorders; 2005 Chapter 28:224 – 244.
3. Finsterer J,. Leigh and Leigh-like syndrome in children and adults . Pediatr Neurol 2008 Oct; 39(4):223-235.
4. OMIM Entry – #308930 – LEIGH SYNDROME, X-LINKED.