Tyrosine, a Amonosäure, is a precursor of several neurotransmitters (eg. As dopamine, norepinephrine, epinephrine), hormones (e.g., thyroxine) and melanin. A lack of enzymes that are involved in the Tyrosinemia, leads to various syndromes.

There are many disorders of the metabolism of phenylalanine and tyrosine metabolism of (see table). See also Procedure in a patient with suspected congenital metabolic disorder and investigation for suspected inherited metabolic disorders.

Tyrosine, a Amonosäure, is a precursor of several neurotransmitters (eg. As dopamine, norepinephrine, epinephrine), hormones (e.g., thyroxine) and melanin. A lack of enzymes that are involved in the Tyrosinemia, leads to various syndromes. There are many disorders of the metabolism of phenylalanine and tyrosine metabolism of (see table). See also Procedure in a patient with suspected congenital metabolic disorder and investigation for suspected inherited metabolic disorders. Metabolic disorders of phenylalanine and tyrosine disease (OMIM number) Defective proteins or enzymes defective gene or genes (chromosomal location) Comments phenylketonuria (PKU), with classical and mild forms (261600) phenylalanine hydroxylase PAH (12q24.1) * Biochemical Profile: Increased phenylalanine in blood Clinical features: mental retardation, behavioral treatment: avoidance of phenylalanine in food intake, tyrosine supplementation Dihydropteridine reductase deficiency (261630) dihydropteridine reductase QDPR (4p15.31) * biochemical profile: Elevated phenylalanine in the blood, in the urine increased biopterin, low biopterin in blood Clinical features: Similar to lighter phenylketonuria, but when the neurotransmitter deficiency is not detected, mental retardation, seizures and dystonia can develop. Treatment: avoidance of phenylalanine in food intake, tyrosine supplementation, folic acid, neurotransmitter replacement pterin 4?-carbinolamine dehydratase deficiency (264070) pterin 4?-carbinolamine dehydratase PCBD (10q22) * biochemical profile: Elevated phenylalanine in the blood, high neopterin and Primapterin in the urine, low blood biopterin Clinical features: Similar to easily phenylketonuria, but when the neurotransmitter deficiency is not detected, mental retardation, seizures and dystonia can develop. Treatment: avoidance of phenylalanine in food intake, tyrosine supplementation, neurotransmitter replacement Biopterinsynthesemangel GTP cyclohydrolase (233910) GCH1 (14q22) * biochemical profile: Elevated phenylalanine in the blood, low biopterin in the urine, low (GCH), or high (PTS and SPR) neopterin in urine Clinical features: Similar to easily phenylketonuria, but when the neurotransmitter deficiency is not detected, mental retardation, seizures and dystonia can develop. Treatment: tetrahydrobiopterin and neurotransmitters supplementation 6-pyruvoyl-tetrahydropterin synthase (261640) PTS (11q22-q23) * sepiapterin reductase (182125) SPR (2p14-p12) * tyrosinemia type I (hepatorenal; 276700) FAH fumarylacetoacetate hydrolase (15q23- q25) * biochemical profile: elevated tyrosine in the blood, increased succinylacetone in blood and urine Clinical features: liver cirrhosis, acute liver failure, peripheral neuropathy, Fanconi syndrome treatment: avoidance of phenylalanine, tyrosine, and methionine in the dietary intake; nitisinone; Liver transplantation tyrosinemia type II (oculocutaneous; 276600) tyrosine aminotransferase TAT (16q22.1-q22.3) * biochemical profile: Elevated tyrosine and phenylalanine in the blood Clinical features: mental retardation, palmoplantar Hyperkeratitis, corneal ulcers treatment: avoidance of phenylalanine and tyrosine in food intake tyrosinemia type III (276,710) of 4-hydroxyphenylpyruvate HPD (12q24-qter) * biochemical profile: elevated tyrosine in the blood, increased 4-hydroxyphenyl derivatives in the urine Clinical features: retardation, seizures, ataxia Behandlun g: avoidance of phenylalanine and tyrosine in the food intake, ascorbate supplementation Transient tyrosinemia of the newborn 4-hydroxyphenylpyruvate non genetically biochemical profile: increased phenylalanine and tyrosine in blood Clinical features: typically occurs in premature infants on, usually asymptomatic Occasionally feeding problems and lethargy: Avoiding of tyrosine in the food intake and ascorbate supplementation only in symptomatic patients Hawkinsinuria (140350) 4-hydroxyphenylpyruvate complex HPD (12q24-qter) * Bioche premix profile: Slight Hypertyrosinämie, increased urine hawkinsin Clinical features: failure to thrive, ketotic metabolic acidosis treatment: avoidance of phenylalanine and tyrosine in the food intake, ascorbate supplementation alkaptonuria (203500) Homogentisatoxidase HGD (3q21-q23) * biochemical profile: Elevated homogentisic acid in the urine clinical features: dark urine, ochronosis, arthritis treatment: No; Ascorbate supplementation to reduce pigmentation Oculocutaneous albinism type I (A and B; 203100) TYR tyrosinase (11q21) * Biochemical Profile: No abnormalities of the amino acids in the blood and urine; Tyrosinase is missing (IA) or is reduced (IB) Clinical features: Missing (IA) or reduced (IB) pigment in the skin, hair, iris and retina; nystagmus; Blindness; Skin cancer treatment: protection of the skin and eyes of actinic radiation * The gene was identified, and the molecular basis has been elucidated. OMIM = Online Mendelian Inheritance in Man (see OMIM database). Transient tyrosinemia of the newborn A temporary immaturity of metabolic enzymes, especially the 4-Hydroxyphenylpyruvatsäuredioxygenase, sometimes (usually in premature infants, particularly those having a high protein diet) leads to increased Tyrosinspiegeln in the blood; Metabolites can be found in the neonateln Routine screening for phenylketonuria (PKU). Most infants are asymptomatic, but some show lethargy and eating disorders. Tyrosinemia can be distinguished from the PKU by elevated Plasmatyrosinspiegel. In most cases, it goes back spontaneously. Patients should a Tyrosinrestriktion (2 g / kg / day) and vitamin C 200-400 mg p.o. once daily. Type I tyrosinemia This autosomal recessive disorder causes a lack of Fumarylacetoacetathydroxylase, an important enzyme for the Tyrosinemia. The disease can manifest as fulminant hepatic failure in the neonatal period or in older infants and children as indolent subclinical hepatitis, painful peripheral neuropathy and disorders of the renal tubules (z. B. metabolic acidosis with normal anion gap, hypophosphatemia, vitamin D-resistant rickets) , Children who do not die in infancy through the associated liver failure, have a significant risk of developing liver cancer. The diagnosis of Type I tyrosinemia is believed at elevated Tyrosinspiegeln and confirmed by high levels of succinylacetone in serum or urine and a low Fumarylacetoacetathydroxylase activity in the blood cells or in liver biopsies. Treatment with nitisinone is successful in acute episodes and slows progression. A phenylalanine and tyrosine diet is recommended. Liver transplantation is effective. Tyrosinemia type II This is a rare autosomal recessive disorder caused by a deficiency of Tyrosintransaminase. An accumulation of tyrosine causes cutaneous and corneal ulcers. The secondary increase in phenylalanine can – although small – untreated cause neuropsychiatric symptoms. The diagnosis of trisomy type II is provided by the increase of tyrosine in serum, a lack of succinylacetone in the serum or urine and measuring a decreased enzyme activity in the liver. The disease is easily treated by restriction of phenylalanine and tyrosine in the diet. Alkaptonurie The rare autosomal recessive disorder caused by the lack of Homogentisatoxidase. Homogentisatoxidase metabolites accumulate in the skin and stain them dark. Kristallpräzipitate precipitate in the joints. This disease is usually diagnosed in adults and causes dark pigmentation of the skin (ochronosis) and arthritis. The urine is dark in the air because oxidize the metabolic products of Homogentinsäure. The diagnosis of Alkaptonurie is provided by the increased levels of Homogentinsäure (> 4-8 g / 24 h). There is no effective treatment for Alkaptonurie, but ascorbic acid 1 g p.o. once a day, the pigment deposition can reduce by renal excretion of Homogentinsäure. Oculocutaneous albinism A lack of tyrosinase results in a lack of skin and Retinapigmentation. This reduces the risk of skin cancer and a significant loss of vision is increased. Nystagmus and photophobia are often present (albinism).

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