congenital lactic acidosis, Saguenay-Lac-Saint-Jean type

Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type (sometimes called French-Canadian Leigh syndrome) is a mitochondrial disorder that mainly affects energy-hungry tissues such as the brain and muscles. It results from pathogenic variants in the LRPPRC gene, which impair the function of mitochondrial complex IV and lead to an accumulation of lactic acid in the body. Symptoms usually begin in the newborn period or early infancy, and both boys and girls can be affected. Because no robust epidemiologic studies have been completed, the precise number of affected individuals worldwide is not known, although the condition was first recognized in families from the Saguenay-Lac-Saint-Jean region of Québec.

The earliest signs are often metabolic, with persistent lactic acidosis that can cause rapid breathing, low blood sugar, and poor feeding in newborns. Hypotonia (low muscle tone) and global developmental delay are common and may be apparent within the first few months of life. Neurological involvement can include seizures, nystagmus, and problems with coordination such as truncal ataxia or dysmetria. Many infants have characteristic facial features such as a prominent forehead or low-set ears, but these can be subtle. Over time, some children develop additional complications, including cardiac findings such as mitral regurgitation or, more rarely, aortic valve malformation. Episodes of metabolic crisis triggered by illness or fasting may lead to worsening acidosis and require emergency care. Less common features reported in a subset of individuals include microcephaly, spasticity, inguinal hernia, or partial absence of the corpus callosum. Not all individuals experience all features, and severity varies considerably between families and even among siblings.

Saguenay-Lac-Saint-Jean type congenital lactic acidosis is caused by biallelic (two-copy) pathogenic variants in the LRPPRC gene. The gene provides instructions for a protein that helps mitochondria produce energy; when the protein is not functional, activity of complex IV (cytochrome c oxidase) drops sharply, leading to the build-up of lactic acid in blood and cerebrospinal fluid. The condition is inherited in an autosomal recessive pattern, meaning a child must receive one altered copy of LRPPRC from each parent to be affected. Parents who each carry a single variant are generally healthy but have a 25 percent chance in each pregnancy of having an affected child, a 50 percent chance of having a carrier child, and a 25 percent chance of having a child who is neither carrier nor affected. The disorder is more likely to appear in families in which the parents share a common ancestor because they have a higher chance of carrying the same rare genetic change. Genetic counseling can help families understand carrier testing, reproductive options, and implications for extended relatives.

Currently, management focuses on supportive care and symptom control because no disease-specific therapies have been approved. Acute metabolic crises are treated promptly with intravenous fluids, correction of acidosis, and avoidance of prolonged fasting. Antiepileptic medications address seizures, and physical and occupational therapies support motor development. Nutritional support, including high-calorie feeds or gastrostomy, may be necessary for infants with feeding difficulties. Because this is a multi-system condition, long-term care is best coordinated by a multidisciplinary team that may include metabolic specialists, neurologists, cardiologists, dietitians, and therapists. Regular surveillance is an essential part of long-term care, helping to identify potential complications such as cardiomyopathy or worsening neurological symptoms before they become serious. Families should discuss individualized monitoring schedules and emerging treatment options with their healthcare team.

Outcomes for individuals with Saguenay-Lac-Saint-Jean type congenital lactic acidosis depend on the frequency and severity of metabolic crises, the degree of neurological involvement, and access to specialized care. Some children experience repeated episodes of severe acidosis that can be life-threatening, whereas others achieve partial stabilization with careful metabolic management. Supportive therapies, early intervention services, and vigilant monitoring can improve quality of life and developmental progress for many families. Severity and symptoms vary widely between individuals. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with metabolic specialists familiar with this condition, join patient support communities, and enroll in natural history registries that track long-term health.