SNP Shot: Genomic Insights

Tyrosinemia is a genetic condition that hinders the body's ability to properly break down tyrosine, an amino acid vital for protein construction. Without intervention, tyrosine and related compounds accumulate in tissues and organs, potentially causing severe health issues.

There are three forms of tyrosinemia, differentiated by their specific symptoms and underlying genetic causes. Tyrosinemia type I represents the most severe form and typically manifests within the first few months of life. Infants affected by this type may exhibit failure to thrive, characterized by poor weight gain and growth, often due to diarrhea and vomiting triggered by protein-rich foods. Other symptoms may include jaundice (yellowing of the skin and eyes), a distinctive cabbage-like odor, and an increased susceptibility to bleeding, particularly nosebleeds.

Further complications of tyrosinemia type I can involve liver and kidney failure, rickets (bone softening and weakening), and an elevated risk of liver cancer (hepatocellular carcinoma). Some children may experience recurrent neurological crises, marked by altered mental state, reduced sensation in the limbs (peripheral neuropathy), abdominal pain, and severe breathing difficulties (respiratory failure). These crises can last for several days. Untreated, tyrosinemia type I often results in a reduced lifespan, with survival beyond the age of 10 being uncommon. However, with timely diagnosis and appropriate treatment, affected individuals can live into adulthood.

Tyrosinemia type II generally emerges in early childhood and impacts the eyes, skin, and cognitive development. Common symptoms include eye pain and redness, excessive tearing, heightened sensitivity to light (photophobia), and thick, painful skin on the palms and soles of the feet (palmoplantar hyperkeratosis). Around half of those with tyrosinemia type II experience some degree of intellectual disability.

Tyrosinemia type III is the rarest form among the three. Its defining characteristics include intellectual disabilities, seizures, and recurrent episodes of balance and coordination loss (intermittent ataxia). Unlike type I, liver problems are not associated with types II and III.

Approximately 1 in 10 newborns experience temporarily elevated tyrosine levels (transient tyrosinemia). These instances are not genetic in origin, and are often due to vitamin C deficiency or liver immaturity, typically linked to premature birth.

Inheritance:

Tyrosinemia follows an autosomal recessive inheritance pattern. This means that for the disorder to develop, an individual must inherit two copies of the mutated gene, one from each parent. The parents, carrying only one copy of the altered gene, are typically asymptomatic carriers of the condition.