Disorders of tyrosine metabolism
- Markus Grompe, MD
Markus Grompe, MD
- Professor of Pediatrics
- Oregon Health Sciences University
- Section Editors
- Sihoun Hahn, MD, PhD
Sihoun Hahn, MD, PhD
- Section Editor — Genetics
- Professor of Pediatrics
- University of Washington School of Medicine, Seattle Children's Hospital
- Elizabeth B Rand, MD
Elizabeth B Rand, MD
- Section Editor — Pediatric Hepatology
- Professor of Pediatrics
- University of Pennsylvania School of Medicine
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 .
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.To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
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- TYROSINE METABOLISM
- HEREDITARY TYROSINEMIA TYPE 1
- HT1 pathophysiology
- HT1 genetics
- HT1 clinical features
- HT1 laboratory diagnosis
- HT1 management
- - Nitisinone
- - Liver transplantation
- HEREDITARY TYROSINEMIA TYPE 2
- HT2 pathophysiology
- HT2 genetics
- HT2 clinical features
- HT2 laboratory diagnosis
- HT2 management
- HEREDITARY TYROSINEMIA TYPE 3
- Clinical features
- ACQUIRED TYROSINEMIA
- Transient tyrosinemia of the newborn
- Hepatocellular dysfunction