There are numerous disorders of phenylalanine and tyrosine metabolism (see the table Phenylalanine and Tyrosine Metabolism Disorders ). See also Approach to the Patient With a Suspected Inherited Disorder of Metabolism Approach to the Patient With a Suspected Inherited Disorder of Metabolism Most inherited disorders of metabolism (inborn errors of metabolism) are rare, and therefore their diagnosis requires a high index of suspicion. Timely diagnosis leads to early treatment and... read more and testing for suspected inherited disorders of metabolism Initial testing Most inherited disorders of metabolism (inborn errors of metabolism) are rare, and therefore their diagnosis requires a high index of suspicion. Timely diagnosis leads to early treatment and... read more .
Transient tyrosinemia of the newborn
Transient immaturity of metabolic enzymes, particularly 4-hydroxyphenylpyruvic acid dioxygenase, sometimes leads to elevated plasma tyrosine levels (usually in premature infants, particularly those receiving high-protein diets); metabolites may show up on routine neonatal screening Screening Tests for Newborns Screening recommendations for newborns vary by clinical context and regulatory requirements. In the United States, the Health Resources & Services Administration recommends screening for all... read more for phenylketonuria Phenylketonuria (PKU) Phenylketonuria is a disorder of amino acid metabolism that causes a clinical syndrome of intellectual disability with cognitive and behavioral abnormalities caused by elevated serum phenylalanine... read more (PKU).
Most infants are asymptomatic, but some have lethargy and poor feeding.
Tyrosinemia is distinguished from PKU by elevated plasma tyrosine levels.
Most cases resolve spontaneously. Symptomatic patients should have dietary tyrosine restriction (2 g/kg/day) and be given vitamin C 200 to 400 mg orally once a day.
Tyrosinemia type I
This disorder is an autosomal recessive Autosomal Recessive Genetic disorders determined by a single gene (Mendelian disorders) are easiest to analyze and the most well understood. If expression of a trait requires only one copy of a gene (one allele)... read more condition caused by deficiency of fumarylacetoacetate hydroxylase, an enzyme important for tyrosine metabolism.
Disease may manifest as fulminant liver failure in the neonatal period or as indolent subclinical hepatitis, painful peripheral neuropathy, and renal tubular disorders (eg, normal anion gap metabolic acidosis Normal anion gap acidosis Metabolic acidosis is primary reduction in bicarbonate (HCO3−), typically with compensatory reduction in carbon dioxide partial pressure (Pco2); pH may be markedly low or slightly... read more , hypophosphatemia Hypophosphatemia Hypophosphatemia is a serum phosphate concentration < 2.5 mg/dL (0.81 mmol/L). Causes include alcohol use disorder, burns, starvation, and diuretic use. Clinical features include muscle weakness... read more , vitamin D–resistant rickets Hypophosphatemic Rickets Hypophosphatemic rickets is a genetic disorder characterized by hypophosphatemia, defective intestinal absorption of calcium, and rickets or osteomalacia unresponsive to vitamin D. It is usually... read more ) in older infants and children. Children who do not die of associated liver failure in infancy have a significant risk of developing liver cancer.
Diagnosis of tyrosinemia type I is suggested by elevated plasma levels of tyrosine; it is confirmed by genetic testing or a high level of succinylacetone in plasma or urine and by low fumarylacetoacetate hydroxylase activity in blood cells or liver biopsy specimens. Treatment with nitisinone (NTBC) is effective in acute episodes and slows progression.
A diet low in phenylalanine and tyrosine is recommended. Liver transplantation is effective.
Tyrosinemia type II
This rare autosomal recessive Autosomal Recessive Genetic disorders determined by a single gene (Mendelian disorders) are easiest to analyze and the most well understood. If expression of a trait requires only one copy of a gene (one allele)... read more disorder is caused by tyrosine transaminase deficiency.
Accumulation of tyrosine causes cutaneous and corneal ulcers. Secondary elevation of phenylalanine, though mild, may cause neuropsychiatric abnormalities if not treated.
Diagnosis of tyrosinemia type II is by elevation of tyrosine in plasma, absence of succinylacetone in plasma or urine, and genetic testing; measurement of decreased enzyme activity in liver biopsy is usually not needed.
This disorder is easily treated with mild to moderate restriction of dietary phenylalanine and tyrosine.
This rare autosomal recessive Autosomal Recessive Genetic disorders determined by a single gene (Mendelian disorders) are easiest to analyze and the most well understood. If expression of a trait requires only one copy of a gene (one allele)... read more disorder is caused by homogentisic acid oxidase deficiency; homogentisic acid oxidation products accumulate in and darken skin, and crystals precipitate in joints.
The condition is usually diagnosed in adults and causes dark skin pigmentation (ochronosis) and arthritis. Urine turns dark when exposed to air because of oxidation products of homogentisic acid. Diagnosis of alkaptonuria is by finding elevated urinary levels of homogentisic acid (> 4 to 8 g/24 hours).
There is no effective treatment for alkaptonuria, but ascorbic acid 1 g orally once a day may diminish pigment deposition by increasing renal excretion of homogentisic acid.
Oculocutaneous albinism Albinism Oculocutaneous albinism is an inherited defect in melanin formation that causes diffuse hypopigmentation of the skin, hair, and eyes. Ocular albinism affects the eyes and usually not the skin... read more
Tyrosinase deficiency results in absence of skin and retinal pigmentation, causing a much increased risk of skin cancer and considerable vision loss. Nystagmus is often present, and photophobia is common.
The following is an English-language resource that may be useful. Please note that THE MANUAL is not responsible for the content of this resource.
Online Mendelian Inheritance in Man® (OMIM®) database: Complete gene, molecular, and chromosomal location information
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