Summary about Disease
Tyrosinemia is a group of rare genetic metabolic disorders characterized by the body's inability to properly break down tyrosine, an amino acid. This leads to a buildup of tyrosine and its byproducts in the blood, tissues, and urine, causing various health problems affecting the liver, kidneys, and nervous system. There are three main types: Tyrosinemia type 1 (most severe), Tyrosinemia type 2, and Tyrosinemia type 3 (rarest and mildest).
Symptoms
Symptoms vary depending on the type of tyrosinemia.
Tyrosinemia type 1: Liver failure (jaundice, bleeding problems, swelling), kidney problems, cabbage-like odor, failure to thrive, vomiting, diarrhea, increased risk of liver cancer, neurological crises (seizures, abdominal pain, paralysis).
Tyrosinemia type 2: Eye problems (corneal ulcers, painful sensitivity to light), skin lesions (thickening of the skin on palms and soles), intellectual disability, neurological problems.
Tyrosinemia type 3: Intellectual disability, neurological problems (seizures, loss of coordination), intermittent ataxia.
Causes
Tyrosinemia is caused by mutations in genes that provide instructions for enzymes involved in the tyrosine breakdown pathway. Each type is linked to a specific enzyme deficiency:
Tyrosinemia type 1: Mutation in the FAH gene (fumarylacetoacetate hydrolase deficiency).
Tyrosinemia type 2: Mutation in the TAT gene (tyrosine aminotransferase deficiency).
Tyrosinemia type 3: Mutation in the HPD gene (4-hydroxyphenylpyruvate dioxygenase deficiency). These mutations disrupt the normal functioning of the enzymes, leading to the accumulation of tyrosine and its toxic byproducts. It is inherited in an autosomal recessive pattern, meaning both parents must carry a copy of the mutated gene for a child to be affected.
Medicine Used
Tyrosinemia type 1: Nitisinone (Orfadin) is the primary medication used. It inhibits an enzyme upstream in the tyrosine degradation pathway, preventing the buildup of toxic byproducts. Liver transplant may be required in some cases, especially before Nitisinone treatment was widely available.
Tyrosinemia type 2: Dietary restriction of phenylalanine and tyrosine.
Tyrosinemia type 3: Dietary restriction of phenylalanine and tyrosine.
Is Communicable
No, tyrosinemia is not communicable. It is a genetic disorder, meaning it is caused by inherited gene mutations and cannot be spread from person to person.
Precautions
For individuals with tyrosinemia: Strict adherence to prescribed diet and medication regimens is crucial. Regular monitoring by a metabolic specialist is essential. Avoidance of high-protein foods is typically necessary.
For families with a history of tyrosinemia: Genetic counseling is recommended for individuals planning to have children. Carrier testing can determine if parents are carriers of the mutated gene.
How long does an outbreak last?
Tyrosinemia is not an "outbreak" condition like an infectious disease. It is a chronic genetic disorder that is present from birth. Symptoms may fluctuate in severity over time, but the underlying metabolic defect is always present. Without treatment symptoms will persist.
How is it diagnosed?
Newborn screening: Many regions screen newborns for elevated tyrosine levels in their blood.
Blood and urine tests: Elevated levels of tyrosine and its byproducts can be detected in blood and urine samples. Specific metabolites, such as succinylacetone (in tyrosinemia type 1), are diagnostic.
Genetic testing: Genetic testing can confirm the diagnosis by identifying mutations in the FAH, *TAT*, or *HPD* genes.
Liver function tests: To assess liver damage, especially in tyrosinemia type 1.
Kidney function tests: To assess kidney damage.
Timeline of Symptoms
Tyrosinemia type 1: Can present in infancy with acute liver failure (within the first few months of life). Chronic presentation can occur later in infancy or early childhood with liver and kidney problems. Neurological crises can occur at any age if the condition is not well-managed.
Tyrosinemia type 2: Usually diagnosed in infancy or early childhood with eye and skin problems. Neurological problems and intellectual disability may become apparent over time.
Tyrosinemia type 3: Diagnosis often occurs in childhood with the onset of neurological symptoms or intellectual disability.
Important Considerations
Early diagnosis and treatment are critical, especially for Tyrosinemia type 1, to prevent life-threatening complications such as liver failure and neurological crises.
Lifelong management is required, including dietary restrictions, medication, and regular monitoring.
The specific management plan will vary depending on the type of tyrosinemia and the individual's symptoms and response to treatment.
Liver transplantation may still be considered in some cases of Tyrosinemia type 1 despite Nitisinone availabilty.
Adherence to diet and medication is critical to preventing long-term complications.