MCID: LGH003
MIFTS: 28

Leigh Syndrome, French Canadian Type

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Eye diseases, Metabolic diseases

Aliases & Classifications for Leigh Syndrome, French Canadian Type

MalaCards integrated aliases for Leigh Syndrome, French Canadian Type:

Name: Leigh Syndrome, French Canadian Type 57 53 29 6 40
Leigh Syndrome, French-Canadian Type 57 59 13
Lsfc 57 53 75
Cytochrome C Oxidase Deficiency, French Canadian Type 57 53
Leigh Syndrome, Saguenay-Lac-Saint-Jean Type 57 59
Cox Deficiency, French Canadian Type 57 53
Cytochrome Oxidase Deficiency, Saguenay-Lac-Saint-Jean Type 59
Congenital Lactic Acidosis, Saguenay-Lac-Saint-Jean Type 59
Cytochrome C Oxidase Deficiency, French-Canadian Type 59
Cox Deficiency, Saguenay-Lac-Saint-Jean Type 57
Cox Deficiency, Saguenay Lac Saint Jean Type 53
Leigh Syndrome, Saguenay Lac Saint Jean Type 53
Leigh Syndrome , French Canadian Type 73
Cox Deficiency, French-Canadian Type 59
Leigh Syndrome French-Canadian Type 75
Slsj-Cox Deficiency 59

Characteristics:

Orphanet epidemiological data:

59
congenital lactic acidosis, saguenay-lac-saint-jean type
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal; Age of death: adolescent,late childhood;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
death usually occurs by age 2 years
death often occurs during metabolic/acidotic crisis
first described in the geographically isolated saguenay-lac-saint-jean region of quebec, canada
incidence of 1 in 2,000 in saguenay-lac-saint-jean region
see also leigh syndrome


HPO:

32
leigh syndrome, french canadian type:
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Leigh Syndrome, French Canadian Type

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 70472Disease definitionSaguenay-Lac-St. Jean (SLSJ) type congenital lactic acidosis, a French Canadian form of Leigh syndrome (see this term), is a mitochondrial disease characterized by chronic metabolic acidosis, hypotonia, facial dysmorphism and delayed development.EpidemiologyThe exact prevalence of this disorder is not known. It was first described in Saguenay-Lac-Saint-Jean (Quebec, Canada) where its prevalence at birth is estimated to be 1/2,000. In this region, the prevalence of the genemutation underlying the disorder is estimated to be 1/23 inhabitants, and may be due to a founder effect.Clinical descriptionFacial dysmorphism is characterized by a prominent forehead, wide nasal bridge, hypertelorism, broad anterior fontanelle, midfacial hypoplasia, broad midline, synophrys, and a characteristic arched form of the eyebrows, along with mild hirsutism. There are 3 forms of the disease corresponding to varying degrees of severity: a neonatal form, a classic form and a so-called "survivor" form. The neonatal form is characterized by fulminant acidotic states. The classic form can occur from birth with severe lactic acidosis, or manifest between 14 and 24 months by ataxic gait. This form is associated with episodes of lactic acidosis that can be triggered by physical exertion, emotional stress, infection or a heavy meal, and/or metabolic crises. Patients known as "survivors", i.e. those who have survived several episodes, cross a critical threshold and show less severe symptoms including hypotonia, asthenia, developmental delay (language acquisition and walking) and, in older patients, truncal ataxia, and a characteristic wide-based gait.EtiologySLSJ congenital lactic acidosis is caused by two types of mutations in the LRPPRC gene (2p21). The most frequent is a single A354V mutation. Only one patient has been identified as a heterozygouscarrier of the A354V mutation and the C1277Xdel8 deletion of the same gene. LRPPRC codes for the leucine-rich pentatricopeptide repeat-containing protein and appears to be involved in the transport and stability of mature mitochondrial mRNA. Biochemically, the cytochrome C oxidase enzyme (COX) involved in the respiratory chain was found to be deficient in all patients, but other proteins in the respiratory chain may also be deficient.Diagnostic methodsDiagnosis is based on determination of lactate levels in the blood and cerebrospinal fluid, determination of COX activity in fibroblasts, but is made primarily through identification of the A354V mutation, which confirms the diagnosis.Differential diagnosisDifferential diagnoses include other forms of Leigh syndrome and other possible causes of metabolic acidosis such as MELAS syndrome, glucose-6-phosphate dehydrogenase (G6PD) deficiency, pyruvate dehydrogenase deficiency, and pyruvate carboxylase deficiency (see these terms).Antenatal diagnosisSince the discovery of the underlying mutations in 2003, prenatal diagnosis is offered to couples that have had an affected child.Genetic counselingThe disease follows a monogenic autosomal recessive pattern of inheritance. Genetic counseling can be proposed to couples at risk through identification of heterozygous carriers.Management and treatmentThere is no specific treatment for the disease. A diet with a balanced intake of proteins, carbohydrates and lipids, spread evenly over the day, is recommended in order to reduce the high energy demands of digestion. Rest and strictly complying with the need for sleep are also beneficial.PrognosisIn the neonatal form, the prognosis is very poor. In other patients, life expectancy is often less than 5 years due to severe episodes of acidosis.Visit the Orphanet disease page for more resources.

MalaCards based summary : Leigh Syndrome, French Canadian Type, also known as leigh syndrome, french-canadian type, is related to leigh syndrome, and has symptoms including ataxia and tremor. An important gene associated with Leigh Syndrome, French Canadian Type is LRPPRC (Leucine Rich Pentatricopeptide Repeat Containing). Affiliated tissues include liver, skeletal muscle and kidney, and related phenotypes are malar flattening and low anterior hairline

OMIM : 57 The French Canadian type of Leigh syndrome is an autosomal recessive severe neurologic disorder with onset in infancy. Features include delayed psychomotor development, mental retardation, mild dysmorphic facial features, hypotonia, ataxia, and the development of lesions in the brainstem and basal ganglia. Affected individuals tend to have episodic metabolic and/or neurologic crises in early childhood, which often lead to early death (summary by Debray et al., 2011). For a phenotypic description and a discussion of genetic heterogeneity of Leigh syndrome, see 256000. (220111)

UniProtKB/Swiss-Prot : 75 Leigh syndrome French-Canadian type: Severe neurological disorder characterized by bilaterally symmetrical necrotic lesions in subcortical brain regions that is commonly associated with systemic cytochrome c oxidase (COX) deficiency. In the Saguenay-Lac Saint Jean region of Quebec province in Canada, a biochemically distinct form of Leigh syndrome with COX deficiency has been described. Patients have been observed to have a developmental delay, hypotonia, mild facial dysmorphism, chronic well-compensated metabolic acidosis, and high mortality due to episodes of severe acidosis and coma. Enzyme activity was close to normal in kidney and heart, 50% of normal in fibroblasts and skeletal muscle, and nearly absent in brain and liver. LSFC patients show reduced (<30%) levels of LRPPRC in both fibroblast and liver mitochondria and a specifically reduced translation of COX subunits MT-CO1/COXI and MT-CO3 (COXIII).

Related Diseases for Leigh Syndrome, French Canadian Type

Diseases related to Leigh Syndrome, French Canadian Type via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 leigh syndrome 10.0

Symptoms & Phenotypes for Leigh Syndrome, French Canadian Type

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
hypertelorism
strabismus
arched eyebrows

Growth Other:
failure to thrive

Head And Neck Head:
prominent forehead

Laboratory Abnormalities:
increased serum lactate
increased csf lactate
decreased cytochrome c oxidase activity in skin fibroblasts, liver, and skeletal muscle

Muscle Soft Tissue:
hypotonia

Respiratory:
transient tachypnea of the newborn

Neurologic Central Nervous System:
ataxia
tremor
increased csf lactate
developmental delay
hypotonia
more
Head And Neck Nose:
wide nasal bridge
anteverted nares

Metabolic Features:
hypoglycemia
lactic acidosis
metabolic crises
hyperglycemia during crises

Skin Nails Hair Hair:
hirsutism
low frontal hairline
arched eyebrows

Head And Neck Face:
midface hypoplasia
unexpressive facies

Abdomen Liver:
liver biopsy shows increased lipid droplets (microvesicular steatosis)
decreased cytochrome c oxidase activity


Clinical features from OMIM:

220111

Human phenotypes related to Leigh Syndrome, French Canadian Type:

32 (show all 29)
# Description HPO Frequency HPO Source Accession
1 malar flattening 32 HP:0000272
2 low anterior hairline 32 HP:0000294
3 hypertelorism 32 HP:0000316
4 wide nasal bridge 32 HP:0000431
5 anteverted nares 32 HP:0000463
6 strabismus 32 HP:0000486
7 delayed speech and language development 32 HP:0000750
8 hirsutism 32 HP:0001007
9 seizures 32 occasional (7.5%) HP:0001250
10 ataxia 32 HP:0001251
11 muscular hypotonia 32 HP:0001252
12 global developmental delay 32 HP:0001263
13 generalized hypotonia 32 HP:0001290
14 tremor 32 HP:0001337
15 microvesicular hepatic steatosis 32 HP:0001414
16 failure to thrive 32 HP:0001508
17 hypoglycemia 32 HP:0001943
18 increased serum lactate 32 HP:0002151
19 gliosis 32 HP:0002171
20 increased csf lactate 32 HP:0002490
21 highly arched eyebrow 32 HP:0002553
22 tachypnea 32 HP:0002789
23 hyperglycemia 32 HP:0003074
24 lactic acidosis 32 HP:0003128
25 increased hepatocellular lipid droplets 32 HP:0006565
26 cns demyelination 32 HP:0007305
27 peripheral demyelination 32 HP:0011096
28 prominent forehead 32 HP:0011220
29 midface retrusion 32 HP:0011800

UMLS symptoms related to Leigh Syndrome, French Canadian Type:


ataxia, tremor

Drugs & Therapeutics for Leigh Syndrome, French Canadian Type

Search Clinical Trials , NIH Clinical Center for Leigh Syndrome, French Canadian Type

Genetic Tests for Leigh Syndrome, French Canadian Type

Genetic tests related to Leigh Syndrome, French Canadian Type:

# Genetic test Affiliating Genes
1 Leigh Syndrome, French Canadian Type 29 LRPPRC

Anatomical Context for Leigh Syndrome, French Canadian Type

MalaCards organs/tissues related to Leigh Syndrome, French Canadian Type:

41
Liver, Skeletal Muscle, Kidney, Heart, Brain, Skin, Thalamus

Publications for Leigh Syndrome, French Canadian Type

Articles related to Leigh Syndrome, French Canadian Type:

# Title Authors Year
1
Novel LRPPRC Mutation in a Boy With Mild Leigh Syndrome, French-Canadian Type Outside of QuAcbec. ( 29152527 )
2017

Variations for Leigh Syndrome, French Canadian Type

UniProtKB/Swiss-Prot genetic disease variations for Leigh Syndrome, French Canadian Type:

75
# Symbol AA change Variation ID SNP ID
1 LRPPRC p.Ala354Val VAR_018656 rs119466000

ClinVar genetic disease variations for Leigh Syndrome, French Canadian Type:

6
(show all 19)
# Gene Variation Type Significance SNP ID Assembly Location
1 LRPPRC LRPPRC, 8-BP DEL, EXON 35 deletion Pathogenic
2 LRPPRC NM_133259.3(LRPPRC): c.1061C> T (p.Ala354Val) single nucleotide variant Pathogenic rs119466000 GRCh37 Chromosome 2, 44201383: 44201383
3 LRPPRC NM_133259.3(LRPPRC): c.1061C> T (p.Ala354Val) single nucleotide variant Pathogenic rs119466000 GRCh38 Chromosome 2, 43974244: 43974244
4 LRPPRC NM_133259.3(LRPPRC): c.3286delC (p.His1096Thrfs) deletion Likely pathogenic rs797044605 GRCh37 Chromosome 2, 44132909: 44132909
5 LRPPRC NM_133259.3(LRPPRC): c.3286delC (p.His1096Thrfs) deletion Likely pathogenic rs797044605 GRCh38 Chromosome 2, 43905770: 43905770
6 LRPPRC NM_133259.3(LRPPRC): c.3826_3900del single nucleotide variant Pathogenic rs863225443 GRCh37 Chromosome 2, 44123772: 44123772
7 LRPPRC NM_133259.3(LRPPRC): c.3826_3900del single nucleotide variant Pathogenic rs863225443 GRCh38 Chromosome 2, 43896633: 43896633
8 LRPPRC NM_133259.3(LRPPRC): c.2595_2597delGGT (p.Val866del) deletion Pathogenic rs863225444 GRCh38 Chromosome 2, 43934786: 43934788
9 LRPPRC NM_133259.3(LRPPRC): c.2595_2597delGGT (p.Val866del) deletion Pathogenic rs863225444 GRCh37 Chromosome 2, 44161925: 44161927
10 LRPPRC NM_133259.3(LRPPRC): c.2726_2728delAGA (p.Lys909del) deletion Pathogenic rs863225445 GRCh37 Chromosome 2, 44161337: 44161339
11 LRPPRC NM_133259.3(LRPPRC): c.2726_2728delAGA (p.Lys909del) deletion Pathogenic rs863225445 GRCh38 Chromosome 2, 43934198: 43934200
12 LRPPRC NM_133259.3(LRPPRC): c.1489_1582del single nucleotide variant Pathogenic rs863225446 GRCh37 Chromosome 2, 44187673: 44187673
13 LRPPRC NM_133259.3(LRPPRC): c.1489_1582del single nucleotide variant Pathogenic rs863225446 GRCh38 Chromosome 2, 43960534: 43960534
14 LRPPRC NM_133259.3(LRPPRC): c.3147dupA (p.Gly1050Argfs) duplication Pathogenic rs769022521 GRCh37 Chromosome 2, 44145165: 44145165
15 LRPPRC NM_133259.3(LRPPRC): c.3147dupA (p.Gly1050Argfs) duplication Pathogenic rs769022521 GRCh38 Chromosome 2, 43918026: 43918026
16 LRPPRC NM_133259.3(LRPPRC): c.4128delT (p.Glu1377Lysfs) deletion Uncertain significance rs759052246 GRCh37 Chromosome 2, 44116873: 44116873
17 LRPPRC NM_133259.3(LRPPRC): c.4128delT (p.Glu1377Lysfs) deletion Uncertain significance rs759052246 GRCh38 Chromosome 2, 43889734: 43889734
18 LRPPRC NM_133259.3(LRPPRC): c.469+1G> A single nucleotide variant Likely pathogenic rs1060499785 GRCh37 Chromosome 2, 44206964: 44206964
19 LRPPRC NM_133259.3(LRPPRC): c.469+1G> A single nucleotide variant Likely pathogenic rs1060499785 GRCh38 Chromosome 2, 43979825: 43979825

Expression for Leigh Syndrome, French Canadian Type

Search GEO for disease gene expression data for Leigh Syndrome, French Canadian Type.

Pathways for Leigh Syndrome, French Canadian Type

GO Terms for Leigh Syndrome, French Canadian Type

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74 UMLS via Orphanet
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