LSFC
MCID: LGH003
MIFTS: 29

Leigh Syndrome, French Canadian Type (LSFC)

Categories: Eye diseases, Genetic diseases, Metabolic diseases, Neuronal diseases, Rare 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 brain, and related phenotypes are malar flattening and hypertelorism

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 10.2

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

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, Brain, Kidney, Heart, Eye, Cerebellum

Publications for Leigh Syndrome, French Canadian Type

Articles related to Leigh Syndrome, French Canadian Type:

# Title Authors Year
1
Ophthalmic manifestations in patients with Leigh syndrome, French Canadian type. ( 30426811 )
2018
2
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 top 50) (show all 153)
# Gene Variation Type Significance SNP ID Assembly Location
1 LRPPRC NM_133259.3(LRPPRC): c.1061C> T (p.Ala354Val) single nucleotide variant Pathogenic rs119466000 GRCh37 Chromosome 2, 44201383: 44201383
2 LRPPRC NM_133259.3(LRPPRC): c.1061C> T (p.Ala354Val) single nucleotide variant Pathogenic rs119466000 GRCh38 Chromosome 2, 43974244: 43974244
3 LRPPRC LRPPRC, 8-BP DEL, EXON 35 deletion Pathogenic
4 LRPPRC NM_133259.3(LRPPRC): c.3286delC (p.His1096Thrfs) deletion Likely pathogenic rs797044605 GRCh38 Chromosome 2, 43905770: 43905770
5 LRPPRC NM_133259.3(LRPPRC): c.3286delC (p.His1096Thrfs) deletion Likely pathogenic rs797044605 GRCh37 Chromosome 2, 44132909: 44132909
6 LRPPRC NM_133259.3(LRPPRC): c.2966G> A (p.Arg989His) single nucleotide variant Conflicting interpretations of pathogenicity rs774857058 GRCh38 Chromosome 2, 43918329: 43918329
7 LRPPRC NM_133259.3(LRPPRC): c.2966G> A (p.Arg989His) single nucleotide variant Conflicting interpretations of pathogenicity rs774857058 GRCh37 Chromosome 2, 44145468: 44145468
8 LRPPRC NM_133259.3(LRPPRC): c.587A> C (p.Asn196Thr) single nucleotide variant Uncertain significance rs199727887 GRCh37 Chromosome 2, 44204298: 44204298
9 LRPPRC NM_133259.3(LRPPRC): c.587A> C (p.Asn196Thr) single nucleotide variant Uncertain significance rs199727887 GRCh38 Chromosome 2, 43977159: 43977159
10 LRPPRC NM_133259.3(LRPPRC): c.3826_3900del single nucleotide variant Pathogenic rs863225443 GRCh37 Chromosome 2, 44123772: 44123772
11 LRPPRC NM_133259.3(LRPPRC): c.3826_3900del single nucleotide variant Pathogenic rs863225443 GRCh38 Chromosome 2, 43896633: 43896633
12 LRPPRC NM_133259.3(LRPPRC): c.2595_2597delGGT (p.Val866del) deletion Pathogenic rs863225444 GRCh37 Chromosome 2, 44161925: 44161927
13 LRPPRC NM_133259.3(LRPPRC): c.2595_2597delGGT (p.Val866del) deletion Pathogenic rs863225444 GRCh38 Chromosome 2, 43934786: 43934788
14 LRPPRC NM_133259.3(LRPPRC): c.2726_2728delAGA (p.Lys909del) deletion Pathogenic rs863225445 GRCh37 Chromosome 2, 44161337: 44161339
15 LRPPRC NM_133259.3(LRPPRC): c.2726_2728delAGA (p.Lys909del) deletion Pathogenic rs863225445 GRCh38 Chromosome 2, 43934198: 43934200
16 LRPPRC NM_133259.3(LRPPRC): c.1489_1582del single nucleotide variant Uncertain significance rs863225446 GRCh37 Chromosome 2, 44187673: 44187673
17 LRPPRC NM_133259.3(LRPPRC): c.1489_1582del single nucleotide variant Uncertain significance rs863225446 GRCh38 Chromosome 2, 43960534: 43960534
18 LRPPRC NM_133259.3(LRPPRC): c.3147dupA (p.Gly1050Argfs) duplication Pathogenic rs769022521 GRCh37 Chromosome 2, 44145165: 44145165
19 LRPPRC NM_133259.3(LRPPRC): c.3147dupA (p.Gly1050Argfs) duplication Pathogenic rs769022521 GRCh38 Chromosome 2, 43918026: 43918026
20 LRPPRC NM_133259.3(LRPPRC): c.4128delT (p.Glu1377Lysfs) deletion Uncertain significance rs759052246 GRCh38 Chromosome 2, 43889734: 43889734
21 LRPPRC NM_133259.3(LRPPRC): c.4128delT (p.Glu1377Lysfs) deletion Uncertain significance rs759052246 GRCh37 Chromosome 2, 44116873: 44116873
22 LRPPRC NM_133259.3(LRPPRC): c.1369+5G> A single nucleotide variant Uncertain significance rs199628926 GRCh37 Chromosome 2, 44200741: 44200741
23 LRPPRC NM_133259.3(LRPPRC): c.1369+5G> A single nucleotide variant Uncertain significance rs199628926 GRCh38 Chromosome 2, 43973602: 43973602
24 LRPPRC NM_133259.3(LRPPRC): c.130C> G (p.Arg44Gly) single nucleotide variant Uncertain significance rs886056062 GRCh38 Chromosome 2, 43995818: 43995818
25 LRPPRC NM_133259.3(LRPPRC): c.130C> G (p.Arg44Gly) single nucleotide variant Uncertain significance rs886056062 GRCh37 Chromosome 2, 44222957: 44222957
26 LRPPRC NM_133259.3(LRPPRC): c.3430C> T (p.Arg1144Cys) single nucleotide variant Uncertain significance rs760016065 GRCh37 Chromosome 2, 44128598: 44128598
27 LRPPRC NM_133259.3(LRPPRC): c.3430C> T (p.Arg1144Cys) single nucleotide variant Uncertain significance rs760016065 GRCh38 Chromosome 2, 43901459: 43901459
28 LRPPRC NM_133259.3(LRPPRC): c.135C> T (p.Ala45=) single nucleotide variant Conflicting interpretations of pathogenicity rs886056061 GRCh38 Chromosome 2, 43995813: 43995813
29 LRPPRC NM_133259.3(LRPPRC): c.135C> T (p.Ala45=) single nucleotide variant Conflicting interpretations of pathogenicity rs886056061 GRCh37 Chromosome 2, 44222952: 44222952
30 LRPPRC NM_133259.3(LRPPRC): c.96C> T (p.Gly32=) single nucleotide variant Conflicting interpretations of pathogenicity rs886056064 GRCh38 Chromosome 2, 43995852: 43995852
31 LRPPRC NM_133259.3(LRPPRC): c.96C> T (p.Gly32=) single nucleotide variant Conflicting interpretations of pathogenicity rs886056064 GRCh37 Chromosome 2, 44222991: 44222991
32 LRPPRC NM_133259.3(LRPPRC): c.3901-6T> G single nucleotide variant Uncertain significance rs553466522 GRCh37 Chromosome 2, 44121774: 44121774
33 LRPPRC NM_133259.3(LRPPRC): c.3901-6T> G single nucleotide variant Uncertain significance rs553466522 GRCh38 Chromosome 2, 43894635: 43894635
34 LRPPRC NM_133259.3(LRPPRC): c.2385C> T (p.Gly795=) single nucleotide variant Conflicting interpretations of pathogenicity rs886056056 GRCh37 Chromosome 2, 44170945: 44170945
35 LRPPRC NM_133259.3(LRPPRC): c.2385C> T (p.Gly795=) single nucleotide variant Conflicting interpretations of pathogenicity rs886056056 GRCh38 Chromosome 2, 43943806: 43943806
36 LRPPRC NM_133259.3(LRPPRC): c.1343G> T (p.Gly448Val) single nucleotide variant Uncertain significance rs886056058 GRCh37 Chromosome 2, 44200772: 44200772
37 LRPPRC NM_133259.3(LRPPRC): c.1343G> T (p.Gly448Val) single nucleotide variant Uncertain significance rs886056058 GRCh38 Chromosome 2, 43973633: 43973633
38 LRPPRC NM_133259.3(LRPPRC): c.1863T> G (p.Asn621Lys) single nucleotide variant Uncertain significance rs762224854 GRCh37 Chromosome 2, 44175318: 44175318
39 LRPPRC NM_133259.3(LRPPRC): c.1863T> G (p.Asn621Lys) single nucleotide variant Uncertain significance rs762224854 GRCh38 Chromosome 2, 43948179: 43948179
40 LRPPRC NM_133259.3(LRPPRC): c.1419T> C (p.Asp473=) single nucleotide variant Conflicting interpretations of pathogenicity rs886056057 GRCh37 Chromosome 2, 44190796: 44190796
41 LRPPRC NM_133259.3(LRPPRC): c.1419T> C (p.Asp473=) single nucleotide variant Conflicting interpretations of pathogenicity rs886056057 GRCh38 Chromosome 2, 43963657: 43963657
42 LRPPRC NM_133259.3(LRPPRC): c.1649+11C> T single nucleotide variant Likely benign rs200115839 GRCh37 Chromosome 2, 44184513: 44184513
43 LRPPRC NM_133259.3(LRPPRC): c.1649+11C> T single nucleotide variant Likely benign rs200115839 GRCh38 Chromosome 2, 43957374: 43957374
44 LRPPRC NM_133259.3(LRPPRC): c.469+1G> A single nucleotide variant Likely pathogenic rs1060499785 GRCh37 Chromosome 2, 44206964: 44206964
45 LRPPRC NM_133259.3(LRPPRC): c.469+1G> A single nucleotide variant Likely pathogenic rs1060499785 GRCh38 Chromosome 2, 43979825: 43979825
46 LRPPRC NM_133259.3(LRPPRC): c.2981G> C (p.Arg994Thr) single nucleotide variant Uncertain significance rs912716897 GRCh37 Chromosome 2, 44145453: 44145453
47 LRPPRC NM_133259.3(LRPPRC): c.2981G> C (p.Arg994Thr) single nucleotide variant Uncertain significance rs912716897 GRCh38 Chromosome 2, 43918314: 43918314
48 LRPPRC NM_133259.3(LRPPRC): c.592_603delGTGACATACCAG (p.Val198_Gln201del) deletion Uncertain significance rs766285986 GRCh37 Chromosome 2, 44204180: 44204191
49 LRPPRC NM_133259.3(LRPPRC): c.592_603delGTGACATACCAG (p.Val198_Gln201del) deletion Uncertain significance rs766285986 GRCh38 Chromosome 2, 43977041: 43977052
50 LRPPRC NM_133259.3(LRPPRC): c.1253A> C (p.Asn418Thr) single nucleotide variant Uncertain significance rs373908553 GRCh37 Chromosome 2, 44200942: 44200942

Expression for Leigh Syndrome, French Canadian Type

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Pathways for Leigh Syndrome, French Canadian Type

GO Terms for Leigh Syndrome, French Canadian Type

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