Tyrosinemia: Definition, Causes, Types, Symptoms, Diagnosis and Treatment

It is a form of metabolic error of a congenital nature related to acute liver dysfunction during childhood.

Metabolism is a process in which our bodies break down substances as we use them for energy, in this case, tyrosine.

Tyrosine is an amino acid found in most proteins.

People with tyrosinemia cannot break down proteins because the body does not have an enzyme that it needs, fumarylacetoacetate hydrolase, to metabolize tyrosine, and proteins accumulate in their bodies toxic.

What causes progressive damage to the liver and kidneys, mainly in the liver. The liver is usually the principal place where tyrosine is metabolized.

This is a sporadic disease; only one person in 100,000 has it.

Causes of tyrosinemia

Tyrosinemia is a genetic disease inherited in an autosomal recessive manner, which means that to have the condition, the child must inherit two defective genes, one from each parent.


In families where both parents carry the gene, there is a one in four risks that a child will have tyrosinemia.

A genetic test is available, so couples at high risk of being carriers can determine their risk of having a child with tyrosinemia.

In tyrosinemia, the body cannot break down amino acids effectively, resulting in severe kidney and liver dysfunction.

Tyrosinemia types

Tyrosinemia has been classified into three types:

Tyrosinemia type I

Although not a primary disorder of tyrosine metabolism, this disorder is associated with increased levels of tyrosine and its metabolites, which inhibit many transport functions and enzyme activities.

Tyrosinemia type I is the acute form characterized by delayed development, vomiting, diarrhea, a cabbage-like odor, hepatomegaly, fever, jaundice, edema, and progressive liver disease.

Death can occur in the first year of life from liver failure.

Tyrosinemia type II

Symptoms of type II tyrosinemia are mainly oculocutaneous, such as tearing, photophobia, and flushing.

Other signs may include mild corneal herpetiform erosions, dendritic ulcers, and corneal and conjunctival plaques. Prominent neovascularization can also be seen.

There are effects such as corneal scarring, nystagmus, and glaucoma in the long term.

Skin lesions usually begin with or after eye lesions. Findings on the skin may start as painful, non-pruritic blisters or erosions that crust over and become hyperkeratotic.

Mental retardation is an inconsistent feature; Mild to moderate retardation, self-mutilating behavior, fine motor coordination disturbances, and language deficits have been reported. Death occurs during the first decade of life.

There are increased levels of tyrosine in the blood and urine, urinary tests for succinylacetone, and analysis of tissues (liver or fibroblasts) for hepatic phenylalanine hydroxylase activity establish the diagnosis.

This disorder is associated with a deficiency of the liver enzyme tyrosine aminotransferase, the rate-limiting enzyme for tyrosine catabolism.

Tyrosinemia, tyrosinuria, increased urinary phenolic acids, N -acetyl tyrosine, and tyramine persist for life.

The metabolism of other amino acids and kidney and liver function is normal.

Type III or neonatal tyrosinemia

Babies with neonatal tyrosinemia are often passive and may have difficulty swallowing, decreased psycholinguistic skills, reduced motor activity, long-term jaundice, and elevated galactose levels, phenylalanine, histidine, and cholesterol.

Some studies have seen mild acidosis in 50 percent of infants with tyrosinemia.

It is assumed that this disorder is caused by a relative deficiency of p-hydroxyphenylpyruvate oxidase stressed by high protein diets, resulting in high concentrations of tyrosine and phenylalanine.

Others have suggested a slight decrease in the activity of the liver enzyme tyrosine aminotransferase.

Symptoms of tyrosinemia in children

Tyrosinemia symptoms tend to fall into two categories, acute and chronic.

Acute phase

In the acute form of tyrosinemia, babies experience symptoms within a month of birth.

They may not gain weight properly, have an enlarged liver and spleen, and a swollen abdomen, symptoms of other liver diseases.

Jaundice may or may not be prominent. Babies with tyrosinemia also have leg swelling and a greater tendency to bleed, especially nosebleeds.

These babies need liver transplants right away.

Chronic phase

Other children have a form of tyrosinemia with a more gradual onset and less severe symptoms.

Effects on the liver

Enlarged liver and spleen are the main symptoms, the abdomen becomes distended with fluid, and these children also sometimes have trouble gaining weight and have jaundice.

They may vomit or have diarrhea. Liver disease develops more slowly, causing liver failure and eventually leading to cirrhosis.

Kidney effects

Renal effects are tubulopathy, nephromegaly, Fanconi syndrome, and renal failure.

Other symptoms

Other symptoms are splenomegaly or enlarged spleen, cardiomyopathy, heart failure, seizures, and ascites.

These children will also need liver transplants, but not so quickly. Some children can be treated for years, if necessary, before receiving a transplant.

Diagnosis of tyrosinemia

Tyrosinemia is diagnosed based on blood tests and urine tests. Liver function tests are often abnormal in both acute and chronic forms of the disease.

Low serum albumin and clotting factors are also frequently found. Due to the biochemical defect, abnormal products can be measured in the urine that confirms the diagnosis.

Imaging tests may be recommended to learn about:

By ultrasound exams

  • Cardiomegaly (enlarged heart).
  • Enlarged and nodular hepatic hepatomegaly.
  • Splenomegaly enlarged spleen.

By computed tomography and magnetic resonance imaging

  • KidneyRenal size and shape of the kidneys.
  • Cardiomegaly: an enlarged heart.
  • Enlarged and nodular hepatic hepatomegaly.
  • Splenomegaly: enlarged spleen.

A tyrosinemia test can be done while the baby is still developing in the womb.

Doctors can measure succinylacetone or fumarylacetoacetate hydrolase levels in the amniotic fluid. If there is too much fumarylacetoacetate hydrolase, it may mean that the fetus cannot break it down.

Follow-up tests

An increased tyrosine concentration in neonatal screening requires further confirmation and testing as it may be due to other metabolic disorders such as fructose and galactose enzyme deficiencies, giant cell hepatitis, neonatal hemochromatosis, and neonatal infections.

The optimal approach is complex and requires the determination of the concentrations of tyrosine and other amino acids and metabolites in the blood and urine.

Type I tyrosinemia involves elevated urinary succinylacetone concentrations and nonspecific aminoaciduria and requires tissue testing (fibroblasts, erythrocytes, lymphocytes, or liver) for fumarylacetoacetate hydrolase activity.

Type II tyrosinemia involves increased levels of tyrosine only in the blood and urine.

Confirmation of neonatal tyrosinemia depends on elevated levels of tyrosine and phenylalanine.

An early diagnosis can help prevent the risk of mental retardation in children.

Tyrosinemia treatment

Treatment options for tyrosinemia include dietary therapy, liver transplantation, and the pharmacological agent 2- (2-nitro-4-trifluoromethylbenzyl) -1,3-cyclohexanedione.


The first line of defense for treating tyrosinemia is usually a low protein diet. Diet modification is highly vital to treating tyrosinemia.

Tyrosine-rich foods like meats, dairy products, and other protein-rich foods like nuts and beans should be avoided.

Good nutrition and adequate intake of vitamins and minerals do not cure tyrosinemia, but they help children usually grow and minimize protein build-up.

Controlling your diet and providing adequate nutrition may not cure tyrosinemia, but it goes a long way toward maintaining metabolic dysfunction and promoting average growth and development.

The diet should also contain a low concentration of phenylalanine and tyrosine, as it helps to prolong severe liver damage.

In most type III or neonatal tyrosinemia cases, symptoms can be transient and controlled by reducing protein intake or breastfeeding. Some patients respond to ascorbic acid supplementation.

Nitisinone treatment

Nitisinone has also been shown to be effective. Clinical signs and symptoms improve with therapy and diet.

Signs of improvement include a decrease in metabolite concentrations, correction of the secondary abnormality in porphyrin synthesis, progress in the liver and renotubular function, and regression of liver abnormalities by computed tomography.

Correction of porphyrin synthesis reduces the risk of porphyric crises.


Liver transplantation remains the only way to correct tyrosine metabolism.

Today, every child with tyrosinemia needs a new liver sooner or later, depending on the stage of the disease. However, after receiving a transplant, many can lead active and healthy lives.

Rationale and benefits of neonatal screening

Death from complicated liver failure occurs in untreated patients with type I tyrosinemia during the first year of life in an acute form and the first decade of life in a chronic condition.

Hepatocellular carcinoma can also be a cause of death.

The introduction of 2- (2-nitro-4-trifluoromethylbenzyl) -1,3-cyclohexanedione has dramatically changed the outcome of this disorder.

The current indications for liver transplantation in tyrosinemia type I are due to the lack of response to 2- (2-nitro-4-trifluoromethylbenzyl) -1,3-cyclohexanedione, the risk of malignancy, and the decrease in quality of life-related to dietary restriction and frequency of blood sampling.

A successful liver transplant can further reduce the mortality rate in patients who do not respond to 5%.

There is a substantial decrease in the risk of the early development of hepatocellular carcinoma in patients with early and effective therapy.