SNP Shot: Genomic Insights

Citrullinemia is a genetic condition where ammonia and other harmful substances build up in the blood. There are two distinct forms of this disorder, each with unique symptoms and caused by different gene mutations.

Type I citrullinemia, also known as classic citrullinemia, typically manifests within the first few days of life. Infants may initially appear healthy but then develop lethargy, feeding difficulties, vomiting, seizures, and loss of consciousness as ammonia levels rise. Some individuals may also experience severe liver problems. In many cases, type I citrullinemia can be life-threatening. A milder form of type I citrullinemia can emerge later in childhood or adulthood, characterized by intense headaches, blind spots (scotomas), balance and coordination problems (ataxia), and lethargy. Notably, some individuals with the gene mutations for type I citrullinemia may never exhibit any symptoms.

Type II citrullinemia primarily affects the nervous system, leading to symptoms such as confusion, restlessness, memory loss, behavioral changes (including aggression, irritability, and hyperactivity), seizures, and coma. Individuals with this type often exhibit specific food cravings, favoring protein and fat while avoiding carbohydrates. The symptoms of type II citrullinemia usually appear in adulthood and can be triggered by factors like medications, infections, surgery, and alcohol consumption. These adult-onset symptoms can be life-threatening.

Adult-onset type II citrullinemia can also develop in individuals who experienced a liver disorder in infancy called neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), sometimes referred to as neonatal-onset type II citrullinemia. NICCD disrupts the flow of bile from the liver and impairs the body's ability to process certain nutrients. In many cases, NICCD symptoms resolve within a year. However, in rare cases, affected individuals may develop other symptoms in early childhood after seemingly recovering from NICCD. These symptoms include delayed growth, extreme fatigue, specific food preferences (as previously described), and abnormal lipid levels in the blood (dyslipidemia). This condition is known as failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD). Years or even decades later, some individuals with a history of NICCD or FTTDCD may develop the characteristics of adult-onset type II citrullinemia.

Inheritance:

Both type I and type II citrullinemia are inherited in an autosomal recessive manner. This means that an individual must inherit two copies of the mutated gene, one from each parent, to develop the condition. While the parents each carry one copy of the mutated gene, they typically do not exhibit any signs or symptoms of the disorder.