Hypertyrosinemia

Excerpt

Tyrosine is an essential aromatic amino acid required for catecholamines, thyroid hormones, and melanin biosynthesis. Hypertyrosinemia or increased blood tyrosine levels result from an abnormality in tyrosine metabolism. Various acquired and genetic disorders are known to cause hypertyrosinemia. Congenital deficiency of one of the enzymes involved in tyrosine catabolism, immaturity of these enzymes in neonates, or hepatocellular dysfunction can lead to hypertyrosinemia. Accumulation of tyrosine and its toxic metabolites are mainly responsible for disease manifestation.

Acquired forms of hypertyrosinemia are transient, as in neonates, or secondary to liver disease from a different etiology. Hereditary forms are usually more severe and, if untreated, can lead to liver failure, renal tubular acidosis, hepatocellular carcinoma, coagulopathy, seizures, developmental delay, and neurological crisis.

Normal serum tyrosine level ranges from 30 to 120 micromoles/L. However, symptoms do not manifest until serum levels rise above 500 micromoles/L. In most states in the U.S., hereditary tyrosinemias are detected in the newborn screening (NBS) program, which allows for early diagnosis. However, in developing countries, most cases are diagnosed late. Treatment depends on the etiology. Hereditary types would require lifelong tyrosine-restricted diets. Nitisinone, a drug that inhibits toxic metabolite formation, may also be necessary. Liver transplantation is warranted in cases not responding to medical management.