Leigh Syndrome

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OMIM 57 256000 Disease Ontology 12 DOID:3652 ICD10 33 G31.82 MeSH 44 D007888 NCIt 50 C84814 SNOMED-CT 68 29570005 Orphanet 59 ORPHA255210 ORPHA70474

UMLS via Orphanet 74 C2931092 ICD10 via Orphanet 34 G31.8 MedGen 42 C0023264 C1838951 C1850597 C1850598 C1850600 C2931891 more KEGG 37 H01354 SNOMED-CT via HPO 69 258211005 60700002 128602000 22066006 11934000 28835009 16110005 563001 76976005 18963009 271607001 29966009 228156007 247578003 91138005 128613002 246545002 313307000 84757009 91175000 85102008 398151007 398152000 221360009 397790002 8011004 224958001 86854008 36440009 432788009 409623005 359580009 81415000 409622000 190882007 91273001 252157006 255314001 60342002 386806002 more UMLS 73 C0023264 C2931891 C0751267 C0751268 C2931092 more

NINDS : ⁵⁴ Leigh's disease is a rare inherited neurometabolic disorder that affects the central nervous system. This progressive disorder begins in infants between the ages of three months and two years. Rarely, it occurs in teenagers and adults. Leigh's disease can be caused by mutations in mitochondrial DNA or by deficiencies of an enzyme called pyruvate dehydrogenase. Symptoms of Leigh's disease usually progress rapidly. The earliest signs may be poor sucking ability,and the loss of head control and motor skills.These symptoms may be accompanied by loss of appetite, vomiting, irritability, continuous crying, and seizures. As the disorder progresses, symptoms may also include generalized weakness, lack of muscle tone, and episodes of lactic acidosis, which can lead to impairment of respiratory and kidney function.   In Leigh’s disease, genetic mutations in mitochondrial DNA interfere with the energy sources that run cells in an area of the brain that plays a role in motor movements. The primary function of mitochondria is to convert the energy in glucose and fatty acids into a substance called adenosine triphosphate ( ATP). The energy in ATP drives virtually all of a cell's metabolic functions. Genetic mutations in mitochondrial DNA, therefore, result in a chronic lack of energy in these cells, which in turn affects the central nervous system and causes progressive degeneration of motor functions. There is also a form of Leigh’s disease (called X-linked Leigh's disease) which is the result of mutations in a gene that produces another group of substances that are important for cell metabolism. This gene is only found on the X chromosome. 

MalaCards based summary : Leigh Syndrome, also known as leigh disease, is related to mitochondrial dna-associated leigh syndrome and narp and leigh syndrome with leukodystrophy, and has symptoms including ataxia, muscle spasticity and ophthalmoplegia. An important gene associated with Leigh Syndrome is SURF1 (SURF1, Cytochrome C Oxidase Assembly Factor), and among its related pathways/superpathways are Oxidative phosphorylation and Pyruvate metabolism. The drugs Cysteamine and Tocopherol have been mentioned in the context of this disorder. Affiliated tissues include cerebellum, spinal cord and thalamus, and related phenotypes are ptosis and nystagmus

OMIM : ⁵⁷ Leigh syndrome is an early-onset progressive neurodegenerative disorder with a characteristic neuropathology consisting of focal, bilateral lesions in one or more areas of the central nervous system, including the brainstem, thalamus, basal ganglia, cerebellum, and spinal cord. The lesions are areas of demyelination, gliosis, necrosis, spongiosis, or capillary proliferation. Clinical symptoms depend on which areas of the central nervous system are involved. The most common underlying cause is a defect in oxidative phosphorylation (Dahl, 1998). Leigh syndrome may be a feature of a deficiency of any of the mitochondrial respiratory chain complexes: complex I deficiency (252010), complex II deficiency (252011), complex III deficiency (124000), complex IV deficiency (cytochrome c oxidase; 220110), or complex V deficiency (604273). (256000)

UniProtKB/Swiss-Prot : ⁷⁵ Leigh syndrome: An early-onset progressive neurodegenerative disorder characterized by the presence of focal, bilateral lesions in one or more areas of the central nervous system including the brainstem, thalamus, basal ganglia, cerebellum and spinal cord. Clinical features depend on which areas of the central nervous system are involved and include subacute onset of psychomotor retardation, hypotonia, ataxia, weakness, vision loss, eye movement abnormalities, seizures, and dysphagia.

NIH Rare Diseases : ⁵³ Leigh syndrome is a rare, inheritedneurodegenerative condition. It usually becomes apparent in infancy, often after a viral infection. Rarely, it begins in the teenage or adult years. Signs and symptoms usually progress rapidly. Early symptoms may include poor sucking ability; loss of head control and motor skills; loss of appetite; vomiting; and seizures. As the condition progresses, symptoms may include weakness and lack of muscle tone; spasticity; movement disorders; cerebellar ataxia; and peripheral neuropathy. Complications can lead to impairment of respiratory, heart and kidney function. The term "Leigh-like syndrome" is often used for people with features that are strongly suggestive of Leigh syndrome but who do not meet the diagnostic criteria.  The inheritance of Leigh syndrome depends on where the responsible gene is located in each case. This is because it can be due to mutations in either mitochondrial DNA or nuclear DNA:Mitochondrial DNA-associated Leigh syndrome follows a mitochondrial inheritance pattern (also called maternal inheritance). Nuclear gene-encoded Leigh syndrome may be inherited in an autosomal recessive or X-linked manner. Treatment is based on the symptoms present and depends on the type of Leigh syndrome a person has. While life expectancy depends on the cause of Leigh syndrome in each person, most do not survive past mid-childhood or adolescence.

Genetics Home Reference : ²⁵ Leigh syndrome is a severe neurological disorder that usually becomes apparent in the first year of life. This condition is characterized by progressive loss of mental and movement abilities (psychomotor regression) and typically results in death within two to three years, usually due to respiratory failure. A small number of individuals do not develop symptoms until adulthood or have symptoms that worsen more slowly.

Disease Ontology : ¹² A mitochondrial metabolism disease characterized by progressive loss of mental and movement abilities. Symptoms usually begin between ages of three months and two years and include loss of appetite, vomiting, irritability and seizure activity.

Wikipedia : ⁷⁶ Leigh syndrome (also called Leigh disease and subacute necrotizing encephalomyelopathy) is an... more...

Clinical features from OMIM:

256000

#	Description	GenomeRNAi Source Accession	Score	Top Affiliating Genes
1	Increased shRNA abundance (Z-score > 2)	GR00366-A-102	10.15	NDUFS7 COX10
2	Increased shRNA abundance (Z-score > 2)	GR00366-A-107	10.15	NDUFA10 COX10
3	Increased shRNA abundance (Z-score > 2)	GR00366-A-11	10.15	BCS1L NDUFA2
4	Increased shRNA abundance (Z-score > 2)	GR00366-A-114	10.15	NDUFA2
5	Increased shRNA abundance (Z-score > 2)	GR00366-A-115	10.15	NDUFS7 NDUFA9 NDUFA10
6	Increased shRNA abundance (Z-score > 2)	GR00366-A-116	10.15	NDUFS7 NDUFA9 NDUFA10 BCS1L COX10
7	Increased shRNA abundance (Z-score > 2)	GR00366-A-120	10.15	NDUFS7 NDUFA10
8	Increased shRNA abundance (Z-score > 2)	GR00366-A-129	10.15	NDUFA9
9	Increased shRNA abundance (Z-score > 2)	GR00366-A-132	10.15	NDUFA2
10	Increased shRNA abundance (Z-score > 2)	GR00366-A-16	10.15	NDUFS7
11	Increased shRNA abundance (Z-score > 2)	GR00366-A-161	10.15	BCS1L
12	Increased shRNA abundance (Z-score > 2)	GR00366-A-162	10.15	NDUFA2
13	Increased shRNA abundance (Z-score > 2)	GR00366-A-166	10.15	NDUFA9 NDUFA10
14	Increased shRNA abundance (Z-score > 2)	GR00366-A-168	10.15	NDUFA10
15	Increased shRNA abundance (Z-score > 2)	GR00366-A-176	10.15	NDUFA10
16	Increased shRNA abundance (Z-score > 2)	GR00366-A-177	10.15	NDUFS7 NDUFA2
17	Increased shRNA abundance (Z-score > 2)	GR00366-A-183	10.15	NDUFA10
18	Increased shRNA abundance (Z-score > 2)	GR00366-A-54	10.15	BCS1L
19	Increased shRNA abundance (Z-score > 2)	GR00366-A-57	10.15	NDUFS7 NDUFA9 NDUFA10 NDUFA2
20	Increased shRNA abundance (Z-score > 2)	GR00366-A-63	10.15	NDUFA10 BCS1L
21	Increased shRNA abundance (Z-score > 2)	GR00366-A-73	10.15	NDUFA9
22	Increased shRNA abundance (Z-score > 2)	GR00366-A-76	10.15	NDUFA10
23	Increased shRNA abundance (Z-score > 2)	GR00366-A-81	10.15	NDUFA9
24	Increased shRNA abundance (Z-score > 2)	GR00366-A-85	10.15	NDUFA2
25	Increased shRNA abundance (Z-score > 2)	GR00366-A-9	10.15	NDUFA2
26	Increased shRNA abundance (Z-score > 2)	GR00366-A-96	10.15	COX10
27	Decreased shRNA abundance	GR00297-A	9.43	NDUFS7 NDUFS8 SDHA NDUFS3 COX10 NDUFA10

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