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Disorders of tyrosine metabolism

Markus Grompe, MD
Section Editors
Sihoun Hahn, MD, PhD
Elizabeth B Rand, MD
Deputy Editor
Elizabeth TePas, MD, MS


Tyrosine is an aromatic amino acid important in the synthesis of thyroid hormones, catecholamines, and melanin. Impaired catabolism of tyrosine is a feature of several acquired and genetic disorders that may result in elevated plasma tyrosine concentrations [1].


Tyrosine degradation is catalyzed by a series of five enzymatic reactions that yield acetoacetate, which is ketogenic, and the Krebs cycle intermediate fumarate, which is glucogenic (algorithm 1). The hepatocyte and renal proximal tubules are the only two cell types that express the complete pathway and contain sufficient quantities of all enzymes required for tyrosine catabolism.

Four autosomal recessive disorders result from deficiencies in specific enzymes in the tyrosine catabolic pathway: hereditary tyrosinemia (HT) types 1, 2, and 3, and alkaptonuria (AKU). Each disorder is assigned a number on the Online Mendelian Inheritance in Man (OMIM) website. Except for AKU, these disorders result in elevated blood tyrosine levels.

Hypertyrosinemia — Normal plasma tyrosine concentrations are 30 to 120 micromol/L. Values >200 micromol/L are considered elevated. However, clinical manifestations typically do not become apparent until plasma levels exceed 500 micromol/L.

Hypertyrosinemia is detected by quantitative measurement of plasma amino acids. This test usually is performed to evaluate otherwise unexplained liver disease or neurologic abnormalities, such as seizures or developmental delay. Hypertyrosinemia also may be detected on a plasma specimen obtained to investigate elevated urinary tyrosine, seen in the renal Fanconi syndrome (which is manifested by impaired proximal tubular function). HT types 1, 2, and 3 may be detected by expanded newborn metabolic screening available in some states.

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Literature review current through: Nov 2017. | This topic last updated: Dec 20, 2016.
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