Browsing Pathways

Trifunctional protein deficiency is a condition caused by mutations in the genes HADHA and HADHB. The enzyme affected is required to metabolize long-chain fatty acids, which makes a patients ability to convert fats to energy very difficult. This is exacerbated by periods without food. The symptoms associated with this disorder differ depending on when they appear in a patient. In infancy, symptoms would include lethargy, hypoglycaemia and hypotonia. Infants are also at higher risk for sudden death and heart problems. Later onset trifunctional protein deficiency symptoms also include hypotonia, but also include breakdown of muscle tissue and peripheral neuropathy. Treatment includes a low-fat, high-carbohydrate diet and avoiding fasting, as this can induce symptoms of this condition.

Triosephosphate isomerase deficiency is a genetic disorder caused by a mutation in the TPI1 gene. The mutation of this gene causes the production of enzymes that are unstable or enzymes that have reduced activity. This means that cells have reduced energy supplies as glycolysis is compromised. This disorder causes anemia, movement problems and muscle weakness. As a result of the lack of red blood cells to carry oxygen through the body, patients may experience fatigue and shortness of breath. Movement problems appear in early infancy, typically before the age of 2 in patients with this disorder. Treatment includes blood transfusions.

Triosephosphate isomerase deficiency is a genetic disorder caused by a mutation in the TPI1 gene. The mutation of this gene causes the production of enzymes that are unstable or enzymes that have reduced activity. This means that cells have reduced energy supplies as glycolysis is compromised. This disorder causes anemia, movement problems and muscle weakness. As a result of the lack of red blood cells to carry oxygen through the body, patients may experience fatigue and shortness of breath. Movement problems appear in early infancy, typically before the age of 2 in patients with this disorder. Treatment includes blood transfusions.

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.

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.

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 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.