Browsing Pathways

A transient defect in tyrosine metabolism is a common aminoacidopathy in the premature and full-term human infant. This disorder, termed neonatal tyrosinemia, was first described by Levine and Gordon in 1939. In the intervening years other workers have studied this disorder, and have noted the concurrence of tyrosinemia and tyrosyluria. In a current survey of 15,000 infants, 6 mild tyrosinemia occurred during the first week of life in 10% of full-term infants, and severe tyrosinemia occurred in approximately 30% of premature infants. The enzymatic basis of neonatal tyrosinemia is complex and involves the susceptibility of p-hydroxyphenylpyruvic acid oxidase to inhibition in the presence of its substrate, p-hydroxyphenylpyruvic acid and derivatives. The inhibition is reversible by removal of excess substrate and by reducing agents such as ascorbic acid, 2, 6-dichiorophenolindophenol, and a number of hydroquinone and phenylenediamine compounds.

A transient defect in tyrosine metabolism is a common aminoacidopathy in the premature and full-term human infant. This disorder, termed neonatal tyrosinemia, was first described by Levine and Gordon in 1939. In the intervening years other workers have studied this disorder, and have noted the concurrence of tyrosinemia and tyrosyluria. In a current survey of 15,000 infants, 6 mild tyrosinemia occurred during the first week of life in 10% of full-term infants, and severe tyrosinemia occurred in approximately 30% of premature infants. The enzymatic basis of neonatal tyrosinemia is complex and involves the susceptibility of p-hydroxyphenylpyruvic acid oxidase to inhibition in the presence of its substrate, p-hydroxyphenylpyruvic acid and derivatives. The inhibition is reversible by removal of excess substrate and by reducing agents such as ascorbic acid, 2, 6-dichiorophenolindophenol, and a number of hydroquinone and phenylenediamine compounds.

Tyrosinemia type I, also known as fumarylacetoacetase or FAH deficiency, is the most severe type of tyrosinemia, a buildup of tyrosine in the body. It is caused by an autosomal recessive mutation in the the FAH gene that encodes for fumarylacetoacetase, an enzyme that is responsible for the last of five steps that are involved in the metabolic breakdown of tyrosine in the liver and kidneys. The lack of this enzyme's function leads to a buildup of 4-fumarylacetoacetic acid as it couldn't be broken down to fumaric acid and acetoacetic acid. This also leads to an increased concentration of maleylacetoacetic acid. This eventually leads to the increased concentration of L-tyrosine in the body. Symptoms of tyrosinemia type I include jaundice and an enlarged liver, kidney dysfunction, as well as a failure to grow, as foods with high protein and amino acids lead to increased symptoms. Additionally, individuals are more at risk for future liver cancer.

Tyrosinemia type I, also known as fumarylacetoacetase or FAH deficiency, is the most severe type of tyrosinemia, a buildup of tyrosine in the body. It is caused by an autosomal recessive mutation in the the FAH gene that encodes for fumarylacetoacetase, an enzyme that is responsible for the last of five steps that are involved in the metabolic breakdown of tyrosine in the liver and kidneys. The lack of this enzyme's function leads to a buildup of 4-fumarylacetoacetic acid as it couldn't be broken down to fumaric acid and acetoacetic acid. This also leads to an increased concentration of maleylacetoacetic acid. This eventually leads to the increased concentration of L-tyrosine in the body. Symptoms of tyrosinemia type I include jaundice and an enlarged liver, kidney dysfunction, as well as a failure to grow, as foods with high protein and amino acids lead to increased symptoms. Additionally, individuals are more at risk for future liver cancer.

Tyrosinemia type 3, one of the three types of tyrosinemia, is a rare disorder with only a few reported cases. Tyrosinemia type 3 results from a defect in the HPD gene which codes for 4-hydroxyphenylpyruvate dioxygenase. 4-Hydroxyphenylpyruvate dioxygenase plays a role in the catabolism of tyrosine by catalyzing the conversion of 4-hydroxyphenylpyruvate to homogentisate. A defect in this enzyme causes tyrosine and phenylalanine to accumulate in the blood resulting in increased excretion of tyrosine in the urine. Tyrosinemia type 3 symptoms include: seizures, mental retardation and intermittent ataxia (occasional loss of balance and coordination).

Tyrosinemia type 3, one of the three types of tyrosinemia, is a rare disorder with only a few reported cases. Tyrosinemia type 3 results from a defect in the HPD gene which codes for 4-hydroxyphenylpyruvate dioxygenase. 4-Hydroxyphenylpyruvate dioxygenase plays a role in the catabolism of tyrosine by catalyzing the conversion of 4-hydroxyphenylpyruvate to homogentisate. A defect in this enzyme causes tyrosine and phenylalanine to accumulate in the blood resulting in increased excretion of tyrosine in the urine. Tyrosinemia type 3 symptoms include: seizures, mental retardation and intermittent ataxia (occasional loss of balance and coordination).

Tyrosinemia II also known as Richner-Hanhart syndrome is an autosomal recessive disorder caused by a mutation in the TAT gene the encodes for tyrosine aminotransferase. A defect in this enzyme causes excess tyrosine to accumulate in the blood and urine, tyrosine crystals to form in the cornea, and increased excretion in the urine of 4-hydroxyphenylpyruvic acid, hydroxyphenyllactic acid, and p-hydroxyphenylacetic acid. Symptoms commonly appear in early childhood and include: mental retardation, photophobia (increased sensitivity to light), excessive tearing, eye redness and pain and skin lesions of the palms and soles. The patient is treated with restriction of dietary phenylalanine and tyrosine. Sometimes a tyrosine degradation inhibitor is also used to prevents the formation of fumarylacetoacetate from tyrosine. Trosinemia II is commonly misdiagnosed as herpes simplex keratitis.

Tyrosinemia II also known as Richner-Hanhart syndrome is an autosomal recessive disorder caused by a mutation in the TAT gene the encodes for tyrosine aminotransferase. A defect in this enzyme causes excess tyrosine to accumulate in the blood and urine, tyrosine crystals to form in the cornea, and increased excretion in the urine of 4-hydroxyphenylpyruvic acid, hydroxyphenyllactic acid, and p-hydroxyphenylacetic acid. Symptoms commonly appear in early childhood and include: mental retardation, photophobia (increased sensitivity to light), excessive tearing, eye redness and pain and skin lesions of the palms and soles. The patient is treated with restriction of dietary phenylalanine and tyrosine. Sometimes a tyrosine degradation inhibitor is also used to prevents the formation of fumarylacetoacetate from tyrosine. Trosinemia II is commonly misdiagnosed as herpes simplex keratitis.

Tyrosine Hydroxylase (TH) Deficiency is a rare inborn error of metabolism (IEM) and autosomal recessive disorder of catecholamines pathways. The disorder is caused by defects in the Tyrosine hydroxylase (TH) gene which encodes for the enzyme tyrosine hydroxylase. This enzyme is part of the production of catecholamines such as dopamine, norepinephrine and epinephrine are all essential for normal nervous system function. Dopamine transmits signals to help the brain control physical movement and emotional behavior. Norepinephrine and epinephrine are involved in the autonomic nervous system. Mutations in the TH gene result in reduced activity of the tyrosine hydroxylase enzyme. As a result, the body produces less dopamine, norepinephrine and epinephrine. Symptoms of the disorder include abnormal movements, autonomic dysfunction, and other neurological problems. Treatments can include the administration of levodopa; however patient responses can vary greatly. The frequency of Tyrosine Hydroxylase Deficiency is unknown.

Tyrosine Hydroxylase (TH) Deficiency is a rare inborn error of metabolism (IEM) and autosomal recessive disorder of catecholamines pathways. The disorder is caused by defects in the Tyrosine hydroxylase (TH) gene which encodes for the enzyme tyrosine hydroxylase. This enzyme is part of the production of catecholamines such as dopamine, norepinephrine and epinephrine are all essential for normal nervous system function. Dopamine transmits signals to help the brain control physical movement and emotional behavior. Norepinephrine and epinephrine are involved in the autonomic nervous system. Mutations in the TH gene result in reduced activity of the tyrosine hydroxylase enzyme. As a result, the body produces less dopamine, norepinephrine and epinephrine. Symptoms of the disorder include abnormal movements, autonomic dysfunction, and other neurological problems. Treatments can include the administration of levodopa; however patient responses can vary greatly. The frequency of Tyrosine Hydroxylase Deficiency is unknown.