Leigh Syndrome, French Canadian Type

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OMIM 57 220111 Orphanet 59 ORPHA70472 UMLS via Orphanet 74 C1857355 ICD10 via Orphanet 34 G31.8

MedGen 42 C1857355 SNOMED-CT via HPO 69 258211005 194021007 22006008 249321001 708670007 128602000 22066006 162294008 229721007 29164008 62415009 399939002 128613002 246545002 313307000 84757009 91175000 85102008 398151007 398152000 224958001 26079004 36440009 432788009 237630007 271327008 302866003 359580009 81415000 271823003 237598005 80394007 190882007 91273001 more UMLS 73 C1857355

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).

Clinical features from OMIM:

220111

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

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