Tyrosinemia

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Tyrosinemia
L-Tyrosine
Synonyms	N/A
Pronounce	N/A
Specialty	N/A
Symptoms	Failure to thrive, vomiting, diarrhea, jaundice, hepatomegaly, renal tubular dysfunction
Complications	Liver failure, renal failure, neurological crises, hepatocellular carcinoma
Onset	Infancy or early childhood
Duration	Lifelong
Types	Type I (hepatorenal), Type II (oculocutaneous), Type III (neurological)
Causes	Genetic mutation in FAH, TAT, or HPD genes
Risks	Consanguinity, family history
Diagnosis	Blood test, urine test, genetic testing
Differential diagnosis	Galactosemia, hereditary fructose intolerance, citrullinemia
Prevention	N/A
Treatment	Dietary restriction, nitisinone, liver transplantation
Medication	Nitisinone
Prognosis	Variable, depends on type and treatment
Frequency	Rare
Deaths	N/A

A genetic disorder affecting tyrosine metabolism

Diagram showing inborn errors of metabolism related to phenylalanine and tyrosine

Tyrosinemia is a genetic disorder characterized by elevated levels of the amino acid tyrosine in the blood. This condition is caused by a deficiency in one of the enzymes responsible for the breakdown of tyrosine, leading to its accumulation and associated health problems.

Types

There are three main types of tyrosinemia, each caused by a deficiency in a different enzyme involved in tyrosine metabolism:

• Tyrosinemia type I (hepatorenal tyrosinemia) is the most severe form and is caused by a deficiency of the enzyme fumarylacetoacetate hydrolase (FAH). This type can lead to liver and kidney failure, as well as neurological problems.
• Tyrosinemia type II (oculocutaneous tyrosinemia) is caused by a deficiency of the enzyme tyrosine aminotransferase (TAT). It primarily affects the eyes, skin, and mental development.
• Tyrosinemia type III is the rarest form and is caused by a deficiency of the enzyme 4-hydroxyphenylpyruvate dioxygenase (HPD). It can lead to neurological problems.

Genetics

Tyrosinemia is inherited in an autosomal recessive pattern.

Tyrosinemia is inherited in an autosomal recessive pattern, meaning that an individual must inherit two copies of the defective gene, one from each parent, to be affected by the disorder. Carriers, who have only one copy of the mutated gene, typically do not show symptoms.

Pathophysiology

The accumulation of tyrosine and its metabolites in the body can lead to a variety of symptoms and complications, depending on the type of tyrosinemia. In type I, the accumulation of toxic metabolites can cause severe liver and kidney damage. In type II, the buildup of tyrosine affects the eyes and skin, while in type III, neurological issues are more prominent.

Diagnosis

Diagnosis of tyrosinemia is typically made through blood and urine tests that measure the levels of tyrosine and its metabolites. Genetic testing can confirm the specific enzyme deficiency and type of tyrosinemia.

Treatment

Treatment for tyrosinemia varies depending on the type but often includes dietary restrictions to limit tyrosine intake. For type I, the drug nitisinone (NTBC) is used to block the formation of toxic metabolites. Liver transplantation may be necessary in severe cases.

Prognosis

With early diagnosis and appropriate treatment, individuals with tyrosinemia can lead relatively normal lives. However, untreated tyrosinemia, especially type I, can lead to severe complications and reduced life expectancy.

See also

• Phenylketonuria
• Alkaptonuria
• Maple syrup urine disease