Find information on thousands of medical conditions and prescription drugs.


Tyrosinemia (or "Tyrosinaemia") is an error of metabolism, usually inborn, in which the body can not effectively break down the amino acid tyrosine, found in most animal and plant proteins. Tyrosinemia is inherited in an autosomal recessive pattern. There are three types of tyrosinemia, each with distinctive symptoms and caused by the deficiency of a different enzyme. more...

Talipes equinovarus
TAR syndrome
Tardive dyskinesia
Tarsal tunnel syndrome
Tay syndrome ichthyosis
Tay-Sachs disease
Thalassemia major
Thalassemia minor
Thoracic outlet syndrome
Thyroid cancer
Tick paralysis
Tick-borne encephalitis
Tietz syndrome
Todd's paralysis
Tourette syndrome
Toxic shock syndrome
Tracheoesophageal fistula
Transient Global Amnesia
Transposition of great...
Transverse myelitis
Treacher Collins syndrome
Tremor hereditary essential
Tricuspid atresia
Trigeminal neuralgia
Trigger thumb
Triplo X Syndrome
Tropical sprue
Tuberous Sclerosis
Turcot syndrome
Turner's syndrome


Type I tyrosinemia

Type I tyrosinemia (OMIM 276700) is the most severe form of this disorder and is caused by a shortage of the enzyme fumarylacetoacetate hydrolase (EC, encoded by the gene FAH. Fumarylacetoacetate hydrolase is the last in a series of five enzymes needed to break down tyrosine. Symptoms of type I tyrosinemia usually appear in the first few months of life and include failure to gain weight and grow at the expected rate (failure to thrive), diarrhea, vomiting, yellowing of the skin and whites of the eyes (jaundice), cabbagelike odor, and increased tendency to bleed (particularly nosebleeds). Type I tyrosinemia can lead to liver and kidney failure, problems affecting the nervous system, and an increased risk of liver cancer.

Worldwide, type I tyrosinemia affects about 1 person in 100,000. This type of tyrosinemia is much more common in Quebec, Canada. The overall incidence in Quebec is about 1 in 16,000 individuals. In the Saguenay-Lac St. Jean region of Quebec, type 1 tyrosinemia affects 1 person in 1,846.

Type II tyrosinemia

Type II tyrosinemia (OMIM 276600) is caused by a deficiency of the enzyme tyrosine aminotransferase (EC, encoded by the gene TAT. Tyrosine aminotransferase is the first in a series of five enzymes that converts tyrosine to smaller molecules, which are excreted by the kidneys or used in reactions that produce energy. This form of the disorder can affect the eyes, skin, and mental development. Symptoms often begin in early childhood and include excessive tearing, abnormal sensitivity to light (photophobia), eye pain and redness, and painful skin lesions on the palms and soles. About half of individuals with type II tyrosinemia are also mentally retarded. Type II tyrosinemia occurs in fewer than 1 in 250,000 individuals.

Type III tyrosinemia

Type III tyrosinemia (OMIM 276710) is a rare disorder caused by a deficiency of the enzyme 4-hydroxyphenylpyruvate dioxygenase (EC, encoded by the gene HPD. This enzyme is abundant in the liver, and smaller amounts are found in the kidneys. It is one of a series of enzymes needed to break down tyrosine. Specifically, 4-hydroxyphenylpyruvate dioxygenase converts a tyrosine byproduct called 4-hydroxyphenylpyruvate to homogentisic acid. Characteristic features of type III tyrosinemia include mild mental retardation, seizures, and periodic loss of balance and coordination (intermittent ataxia). Type III tyrosinemia is very rare; only a few cases have been reported.


Treatment varies depending on the specific type. A low protein diet may be required in the management of tyrosinemia.


[List your site here Free!]

From Gale Encyclopedia of Medicine, 4/6/01 by John T. Lohr


Phenylketonuria (PKU) is a rare, inherited, metabolic disorder that can result in mental retardation and other neurological problems. People with this disease have difficulty breaking down and using (metabolizing) the amino acid phenylalanine. PKU is sometimes called Folling's disease in honor of Dr. Asbjorn Folling who first described it in 1934.


Phenylalanine is an essential amino acid. These substances are called "essential" because the body must get them from food to build the proteins that make up its tissues and keep them working. Therefore, phenylalanine is required for normal development. Phenylalanine is a common amino acid and is found in all natural foods. However, natural foods contain more phenylalanine than required for normal development. This level is too high for patients with PKU, making a special low-phenylalanine diet a requirement.

The incidence of PKU is approximately one in every 15,000 births (1/15,000). There are areas in the world where the incidence is much higher, particularly Ireland and western Scotland. In Ireland the incidence of PKU is 1/4,500 births. This is the highest incidence in the world and supports a theory that the genetic defect is very old and of Celtic origin. Countries with very little immigration from Ireland or western Scotland tend to have low rates of PKU. In Finland, the incidence is less than 1/100,000 births. Caucasians in the United States have a PKU incidence of 1/8,000, whereas Blacks have an incidence of 1/50,000.

Related diseases:

Maternal phenylketonuria is a condition in which a high level of phenylalanine in a mother's blood causes mental retardation in her child when in the womb. A woman who has PKU and is not using a special low-phenylalanine diet will have high levels of phenylalanine in her blood. Her high phenylalanine levels will cross the placenta and affect the development of her child. The majority of children born from these pregnancies are mentally retarded and have physical problems, including small head size (microcephaly) and congenital heart disease. Most of these children do not have PKU. There is no treatment for maternal phenylketonuria. Control of maternal phenylalanine levels is thought to limit the effects of maternal phenylketonuria.

Hyperphenylalaninemia is a condition in which patients have high levels of phenylalanine in their blood, but not as high as seen in patients with classical PKU. There are two forms of hyperphenylalaninemia: mild and severe. In the mild form of the disease, patients have phenylalanine blood levels of less than 10 mg/dl, even when eating a normal diet (0.6-1.5 mg/dl is considered the normal range.). There are few effects from the mild form of the disease. In the severe form of the hyperphenylalaninemia, patients have higher levels of phenylalanine in their blood. The severe form is distinguished from classical PKU by testing for the presence of phenylalanine hydroxylase (an enzyme that breaks down phenylalanine) in the liver. Classic PKU patients lack this enzyme in their liver, while patients with severe hyperphenylalaninemia have some enzyme activity, but at greatly reduced levels compared with normal persons. Patients with severe hyperphenylalaninemia are treated with the same diet as classical PKU patients.

Tyrosinemia is characterized by a high levels of two amino acids in the blood, phenylalanine and tyrosine. Patients with this disease have many of the same symptoms as seen in classical PKU, including mental retardation. Treatment consists of a special diet similar to the diet for PKU. The main difference between the two diets is that patients with tyrosinemia must eat a diet that is low in both phenylalanine and tyrosine.

Tetrahydrobiopterin deficiency disease is another metabolic disorder. Patients with this disease also have high levels of phenylalanine in their blood. Although phenylalanine levels can be controlled by diet, these patients still suffer from mental retardation because they do not make enough of the neurotransmitters dopamine and serotonin, which are essential for proper neurologic function.

Causes & symptoms

The underlying cause of PKU is mutation in the gene that tells the body to make the enzyme phenylalanine hydroxylase. This enzyme allows the body to break down phenylalanine and ultimately use it to build proteins. Normally, the first step in phenylalanine metabolism is conversion to tyrosine, another amino acid. The genetic mutations result in no enzyme or poor quality enzyme being made. As a consequence, phenylalanine is not converted and builds up in the body. The high levels of phenylalanine can be detected in the blood and urine.

PKU is an autosomal recessive genetic disease. A child must inherit defective genes from both parents to develop PKU. A person with one defective gene and one good gene will develop normally because the good gene will make sufficient phenylalanine hydroxylase. People with one good gene are called carriers because they don't have the disease, but are capable of passing the defective gene on to their children.

If both parents are carriers of defective phenylalanine hydroxylase genes, then the chances of their child having PKU is one in four or 25%. The chances that their child will be a carrier is two in four, or 50%. These percentages hold for each pregnancy.

The gene for phenylalanine hydroxylase is found on chromosome 12. There are many different mutation sites on the gene for phenylalanine hydroxylase. The mutations lead to a range of errors in the enzyme, including lack of the enzyme. The exact mechanism by which excess phenylalanine causes mental retardation is not known.

Children with PKU appear normal at birth, but develop irreversible mental retardation unless treated early. Treatment consists of a special diet that contains very little phenylalanine. This diet must be used throughout the patient's life. Untreated newborns develop disease symptoms at age three to five months. At first they appear to be less attentive and may have problems eating. By one year of age, they are mentally retarded.

Patients with PKU tend to have lighter colored skin, hair, and eyes than other family members. They are also likely to have eczema and seizures. PKU patients have a variety of neurologic symptoms. Approximately 75-90% of PKU patients have abnormal electrocardiograms (ECGs), which measure the activity of their heart. Their sweat and urine may have a "mousy" smell that is caused by phenylacetic acid, a byproduct of phenylalanine metabolism. Untreated PKU children tend to be hyperactive and demonstrate loss of contact with reality (psychosis).


PKU must be detected shortly after birth. Although children with PKU appear normal at birth, they already have high phenylalanine levels. Screening is the only way to detect PKU before symptoms start to develop. In many areas of the world, screening newborns for PKU is performed routinely. The test is typically performed between one and seven days after birth. Blood is obtained by pricking the heel of the newborn and analyzing it for phenylalanine concentration. Very high levels of phenylalanine indicate that there is a problem with phenylalanine hydroxylase. There is no established level of phenylalanine that is considered diagnostic for PKU. Blood levels above 20 mg/dl are generally associated with classical PKU. The generally accepted upper limit for normal in newborns is 2 mg/dl, with most unaffected children having levels below 1 mg/dl. Patients with high blood levels of phenylalanine are tested further to distinguish between classic PKU and related diseases.

The Guthrie Inhibition Assay is usually used to test for blood phenylalanine levels. (An assay compares samples from the body to a reference standard of known concentration to determine the relative strength of the substance in the samples.) The test uses a special strain of the bacterium Bacillus subtilis that requires phenylalanine for growth. The bacterium is grown on the surface of a special medium that lacks phenylalanine. Paper disks containing blood samples and testing standards are placed on top of the agar plate, and the bacteria are allowed to grow. The amount of growth around each disk is proportional to the amount of phenylalanine in the disk. A second assay detects high levels of phenylalanine metabolites in the urine. (These metabolites are the products of phenylalanine when it's broken down and used by the body.) These metabolites first appear four to six weeks after birth and are detected by the addition of a few drops of a 10% ferric chloride solution to a urine sample. If the metabolites are present, a deep bluish green color develops. Color development indicates that the patient has PKU.

Prenatal diagnosis can be done for families with a history of PKU. The test is performed by collecting amniotic or chorionic villus cells and analyzing the DNA for the presence of genetic mutations indicative of PKU. Amniotic fluid cells are collected by inserting a needle through a woman's abdomen and womb and withdrawing some of the amniotic fluid that surrounds the fetus. Chorionic villus cells are obtained by inserting a catheter through the cervix and into the outer membrane that surrounds the uterus.


The only treatment for persons with PKU is to limit the amount of phenylalanine in their diet. PKU patients should eat a special diet that is low in phenylalanine. The diet has small amounts of phenylalanine because it is essential for normal growth and development. The diet should be started before the fourth week of life to prevent mental retardation. If started early enough, the diet is 75% effective in preventing severe mental retardation. Many natural foods, including breast milk, must be avoided because they contain more phenylalanine than PKU patients can tolerate. However, low protein, natural foods, including fruits, vegetables, and some cereals, are acceptable on the diet. Monitoring of blood phenylalanine levels must be done to ensure that normal levels are maintained.

Patients who make a small amount of phenylalanine hydroxylase can eat a limited amount of regular food if their phenylalanine levels remain within an acceptable range. Low-phenylalanine and phenylalanine-free foods are available commercially. The special diet must be used throughout the patient's life. At one time it was thought acceptable to stop the diet when the brain was fully developed. However, reports of decreases in IQ and development of learning and behavior problems in patients who stopped the diet have essentially ended this practice.

Key Terms

Amino acids
The building blocks of protein.
The sum of the many processes by which the body uses food and energy to build tissues and carry out the functions of life.
One of the amino acids that the body must take in through food in order to build the proteins needed for normal growth and functioning.

Further Reading

For Your Information


  • "Education of Students with Phenylketonuria (PKU)." National Institutes of Health
  • "Endocrine and Metabolic Disorders." The Merck Manual.
  • "Phenylketonuria."

Gale Encyclopedia of Medicine. Gale Research, 1999.

Return to Tyrosinemia
Home Contact Resources Exchange Links ebay