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The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
Orpha Number: 70472
Saguenay-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.
The 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 gene mutation underlying the disorder is estimated to be 1/23 inhabitants, and may be due to a founder effect.
Facial 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.
SLSJ 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 heterozygous carrier 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.
Diagnosis 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 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).
Since the discovery of the underlying mutations in 2003, prenatal diagnosis is offered to couples that have had an affected child.
The 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 treatment
There 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.
In 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.
Source: GARD Last updated on 05-01-20
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