Tyrosinemia type 2 is an inborn error of tyrosine metabolism characterized by hypertyrosinemia with oculocutaneous manifestations and, in some cases, intellectual deficit. Prevalence is unknown but less than 150 cases have been reported in the literature so far. The disease appears to be more common in Arab and Mediterranean populations. Skin lesions occur in 80% of cases, ocular involvement in 75% of cases and neurologic findings and some degree of intellectual deficit in up to 60% of cases. Onset is variable but the ocular symptoms (redness, photophobia, excessive tearing and pain) usually develop in the first year of life. Ocular signs include corneal clouding with bilateral dendritiform corneal lesions (pseudodendritic keratitis), neovascularization, corneal ulceration and scarring, which may lead to decreased visual acuity. Cutaneous manifestations usually begin after the first year of life but may develop at the same time as the ocular symptoms. The skin lesions consist of nonpruritic, hyperkeratotic papules and plaques principally located on the palms and soles (palmoplantar hyperkeratosis). These lesions are painful and progressive and are often associated with hyperhidrosis. Central nervous system (CNS) involvement is highly variable with intellectual deficit (ranging from mild to severe) being the most common manifestation. Other signs of CNS involvement include behavioral problems, nystagmus, tremor, ataxia, and convulsions. Tyrosinemia type 2 is transmitted as an autosomal recessive trait and is caused by mutations in the TAT gene (16q22.1) encoding tyrosine aminotransferase (TAT). The elevated levels of tyrosine caused by TAT deficiency appear to result in deposition of tyrosine crystals leading to an inflammatory response and the oculocutaneous findings. It has also been suggested that there is a correlation between the extent of the CNS involvement and the levels of tyrosine in the plasma. Diagnosis is established on the basis of the clinical findings and detection of high levels of plasma and urinary tyrosine, and elevated levels of urinary tyrosine metabolites (such as 4-hydroxyphenylpyruvate, 4-hydroxyphenyllactate, 4-hydroxyphenylacetate and N-acetyltyrosine). TAT assays on liver biopsy samples are usually not necessary for diagnosis. Some patients with tyrosinemia type 2 may be identified through neonatal screening program studies. As the ocular findings are often the initial manifestations of the disease, the pseudodendritic keratitis is often mistaken for herpes simplex keratitis (see this term). Molecular genetic prenatal diagnosis has been reported in families in which the TAT mutation had already been identified. Management revolves around dietary restriction of phenylalanine and tyrosine. Oral retinoids may also be administered for treatment of the skin lesions. The controlled diet results in lowering of plasma tyrosine levels and rapid resolution of the oculocutaneous manifestations. However, the extent to which this controlled diet prevents the CNS involvement is unclear.
Last update: November 2010