Phenylalanine and Tyrosine Metabolism Disorders
Disease (OMIM Number) | Defective Proteins or Enzymes | Comments |
|---|---|---|
Phenylketonuria (PKU), with classic and mild forms (261600*) | Phenylalanine hydroxylase | Biochemical profile: Elevated plasma phenylalanine Clinical features: Intellectual disability, behavioral problems Treatment: Dietary phenylalanine restriction, tyrosine supplementation |
Dihydropteridine reductase deficiency (261630*) | Dihydropteridine reductase | Biochemical profile: Elevated plasma phenylalanine, high urine biopterin, low plasma biopterin Clinical features: Similar to mild PKU, but if neurotransmitter deficiency is unrecognized, development of intellectual disability, seizures, and dystonia Treatment: Dietary phenylalanine restriction, tyrosine supplementation, folinic acid, neurotransmitter replacement |
Pterin-4alpha-carbinolamine dehydratase deficiency (264070*) | Pterin-4alpha-carbinolamine dehydratase | Biochemical profile: Elevated plasma phenylalanine, high urine neopterin and primapterin, low plasma biopterin Clinical features: Similar to mild PKU, but if neurotransmitter deficiency is unrecognized, development of intellectual disability, seizures, and dystonia Treatment: Dietary phenylalanine restriction, tyrosine supplementation, neurotransmitter replacement |
Biopterin synthesis deficiency | GTP-cyclohydrolase (233910*) | Biochemical profile: Elevated plasma phenylalanine, low urine biopterin, low (GCH) or high (PTS and SPR) urine neopterin Clinical features: Similar to mild PKU, but if neurotransmitter deficiency is unrecognized, development of intellectual disability, seizures, and dystonia Treatment: Tetrahydrobiopterin and neurotransmitter supplementation |
6-Pyruvoyl-tetrahydropterin synthase (261640*) | ||
Sepiapterin reductase (182125*) | ||
Tyrosinemia type I (hepatorenal; 276700*) | Fumarylacetoacetate hydrolase | Biochemical profile: Elevated plasma tyrosine, elevated plasma and urinary succinylacetone Clinical features: Cirrhosis, acute liver failure, peripheral neuropathy, Fanconi syndrome Treatment: |
Tyrosinemia type II (oculocutaneous; 276600*) | Tyrosine aminotransferase | Biochemical profile: Elevated plasma tyrosine and phenylalanine Clinical features: Intellectual disability, palmoplantar hyperkeratitis, corneal ulcers Treatment: Dietary phenylalanine and tyrosine restriction |
Tyrosinemia type III (276710, 609695*) | 4-Hydroxyphenylpyruvate dioxygenase | Biochemical profile: Elevated plasma tyrosine, elevated urinary 4-hydroxyphenyl derivatives Clinical features: Developmental delay, seizures, ataxia Treatment: Dietary phenylalanine and tyrosine restriction, ascorbate supplementation |
4-Hydroxyphenylpyruvate dioxygenase | Biochemical profile: Elevated plasma phenylalanine and tyrosine Clinical features: Usually occurring in preterm infants; mostly asymptomatic Occasionally poor feeding and lethargy Treatment: Tyrosine restriction and ascorbate supplementation for symptomatic patients only | |
Hawkinsinuria (140350*) | 4-Hydroxyphenylpyruvate dioxygenase complex | Biochemical profile: Mild hypertyrosinemia, elevated urinary hawkinsin Clinical features: Failure to thrive, ketotic metabolic acidosis Treatment: Dietary phenylalanine and tyrosine restriction, ascorbate supplementation |
Alkaptonuria (203500*) | Homogentisate oxidase | Biochemical profile: Elevated urine homogentisic acid Clinical features: Dark urine, ochronosis, arthritis Treatment: None; ascorbate supplementation to reduce pigmentation |
Oculocutaneous albinism type I (A and B; 203100*) | Tyrosinase | Biochemical profile: No abnormality in plasma and urine amino acids, absent (IA) or decreased (IB) tyrosinase Clinical features: Absent (IA) or decreased (IB) pigment in skin, hair, iris, and retina; nystagmus; blindness; skin cancer Treatment: Protection of skin and eyes from actinic radiation |
* For complete gene, molecular, and chromosomal location information, see the Online Mendelian Inheritance in Man (OMIM) database. | ||