Clinical Guidance

Tyrosinemia type II is characterized by corneal dystrophy, painful palmoplantar hyperkeratosis, and variable intellectual disability. Individuals diagnosed and treated from early infancy may be asymptomatic or have only mild ocular and skin manifestations. Individuals with delayed diagnosis or lack of treatment present with ocular, skin, and variable cognitive manifestations . To date, more than 70 individuals have been identified with tyrosinemia type II . The following description of the phenotypic features associated with this condition is based on these reports. Table 2. Select Features of Tyrosinemia Type II

Diagnostic Criteria

No consensus clinical diagnostic criteria for tyrosinemia type II have been published.

Suggestive Findings

Tyrosinemia type II is caused by deficiency of the enzyme tyrosine aminotransferase (TAT) . Tyrosinemia type II should be suspected in individuals with either or . Note: Tyrosinemia type II is not typically included in NBS panels, but may be detected when screening for tyrosinemia type I.

Scenario 1: Abnormal NBS Result

NBS for hepatorenal tyrosinemia (tyrosinemia type I) is typically based on quantification of tyrosine in dried blood spots. Elevated tyrosine above the cutoff reported by the screening laboratory is considered positive and requires follow-up biochemical testing.

Management Guidelines

No clinical practice guidelines for tyrosinemia type II have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder. When tyrosinemia type II is suspected during the diagnostic evaluation due to high levels of tyrosine (typically 500 mol/L and may exceed 1,000 mol/L), metabolic treatment should be initiated immediately . Development and evaluation of treatment plans, training and education of affected individuals and their families, and avoidance of side effects of dietary treatment (i.e., malnutrition, growth failure) require a multidisciplinary approach including multiple subspecialists, with oversight and expertise from a specialized metabolic center and the involvement of a dietitian with specialized training. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with tyrosinemia type II, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 4. Tyrosinemia Type II: Recommended Evaluations Following Initial Diagnosis

Surveillance Guidelines

In addition to regular evaluations by a metabolic specialist and metabolic dietician, the evaluations summarized in are recommended to monitor existing manifestations, the individual's response to targeted therapy and supportive care, and the emergence of new manifestations. Table 6. Tyrosinemia Type II: Recommended Surveillance