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INTRODUCTION

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Tyrosine is derived from the diet, from metabolism of phenylalanine, and from the body’s proteins during catabolic stress. Tyrosine degradation is catalyzed by a series of five enzymatic reactions, with end products being acetoacetate and fumarate. 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 (Figure 17–1). Normal plasma tyrosine concentrations are between 30 and 120 μmol/L. Increased concentrations of tyrosine in plasma are common and may be the result of a primary inherited metabolic disorder, but they may also be secondary. The most common causes are listed in Table 17–1. The primary disorders are all defects in the tyrosine degradation pathway. The first is tyrosine aminotransferase deficiency (tyrosinemia type 2) and the second is 4–hydroxy-phenylpyruvate dioxygenase deficiency (tyrosinemia type 3). The most common disorder in the pathway, however, is a defect of the last enzyme, namely fumarylacetoacetase, which causes tyrosinemia type 1 (also known as hepatorenal tyrosinosis). The most common secondary causes of high plasma tyrosine concentrations are acute liver disease and transient neonatal tyrosinemia.

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TABLE 17-1Causes of Hypertyrosinemia
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Initial Investigations

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Patients with high plasma tyrosine concentrations will generally need the tests listed in Table 17–2. The dietary protein intake should also be assessed. These tests should identify those causes of tyrosinemia that require urgent treatment, namely tyrosinemia type 1 and galactosemia. Further testing will be needed to confirm these diagnoses or to establish the diagnosis of tyrosinemia type 2 or 3. Figure 17–2 gives a diagnostic algorithm for a neonate with a high tyrosine concentration.

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TABLE 17-2Initial Investigations for Elevated Plasma Tyrosine Concentrations
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FIGURE 17-2.

Diagnostic algorithm for neonates with high plasma tyrosine concentrations. Note that there are many other causes of neonatal liver failure besides galactosemia and tyrosinemia type 1. Gal–1–PUT, galactose–1–phosphate uridyltransferase.

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TYROSINEMIA TYPE 1

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Etiology/Pathophysiology
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