Tyrosinemia

Tyrosine is a precursor of some neurotransmitters (eg, dopamine, norepinephrine, epinephrine), hormones (eg, thyroxine), and melanin; deficiency of enzymes involved in their metabolism leads to a number of syndromes.

Transient tyrosinemia of the newborn

Temporary immaturity of enzymes, especially 4-hydroxyphenylpyruvate dioxygenase, sometimes leads to elevated blood tyrosine levels (usually in premature infants, especially those on a high-protein diet); metabolites may be detected during routine newborn screening for phenylketonuria. Most patients are asymptomatic, but some experience lethargy and decreased appetite. Tyrosinemia is differentiated from phenylketonuria by elevated plasma tyrosine levels.

In most cases, spontaneous normalization of tyrosine levels occurs. In patients with clinical symptoms, it is necessary to limit tyrosine intake with food [2 g/(kg x day)] and prescribe vitamin C 200-400 mg orally once a day.

Alkaptonuria

Alkaptonuria is a rare autosomal recessive disorder caused by a deficiency of homogentisic acid oxidase; oxidation products of homogentisic acid accumulate in the skin, darkening it and depositing crystals in the joints. The disorder is usually diagnosed in adults who have dark skin pigmentation (ochronosis) and arthritis. Urine darkens on exposure to air due to oxidation products of homogentisic acid. Diagnosis is based on elevated levels of homogentisic acid in the urine (>4-8 g/24 hours). There is no effective treatment, but ascorbic acid 1 g orally once daily may reduce pigment deposition by increasing renal excretion of homogentisic acid.

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Oculocutaneous albinism

Tyrosinase deficiency results in a lack of pigmentation of the skin and retina, which greatly increases the risk of developing malignant skin tumors, and a significant decrease in vision. Nystagmus is often present, as well as photophobia.

Tyrosinemia type I

Tyrosinemia type I is an autosomal recessive disorder caused by deficiency of fumaryl acetoacetate hydroxylase, an enzyme involved in tyrosine metabolism. The disorder may present as fulminant liver failure in the neonatal period or as indolent subclinical hepatitis, painful peripheral neuropathy, and renal tubular dysfunction (eg, normal anion gap metabolic acidosis, hypophosphatemia, vitamin D-resistant rickets) in later life. Survivors have an increased risk of developing liver cancer.

Diagnosis is suggested by elevated plasma tyrosine levels; confirmation is by high plasma or urinary succinylacetone levels and low fumarylacetoacetate hydroxylase activity in blood cells or liver tissue (biopsy). Treatment with 2(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) is effective in acute episodes and slows progression. A low-phenylalanine, low-tyrosine diet is recommended. Liver transplantation is effective.

Tyrosinemia type II

Tyrosinemia type II is a rare autosomal recessive disorder caused by a deficiency of tyrosine transaminase. Accumulation of tyrosine causes skin and corneal ulcers. Secondary elevations in phenylalanine levels, although mild, may cause neuropsychiatric disturbances if untreated. Diagnosis is based on elevated plasma tyrosine levels, absence of succinylacetone in plasma or urine, and decreased enzyme activity on liver biopsy. Tyrosinemia type II is readily treated with mild to moderate dietary restriction of phenylalanine and tyrosine.