Neonatal tyrosinemia

Figure 30-12. Intermediates in tyrosine catabolism. Carbons are numbered to emphasize their ultimate fate. (a-KG, a-ketoglutarate Glu, glutamate PLP, pyridoxal phosphate.) Circled numerals represent the probable sites of the metabolic defects in type II tyrosinemia neonatal tyrosinemia alkaptonuria and 0 type I tyrosinemia, or tyrosinosis.

The probable metabohc defect in type I tyrosine-mia (tyrosinosis) is at himarylacetoacetate hydrolase (reaction 4, Figure 30-12). Therapy employs a diet low in tyrosine and phenylalanine. Untreated acute and chronic tyrosinosis leads to death from liver failure. Alternate metabolites of tyrosine are also excreted in type II tyrosinemia (Richner-Hanhart syndrome), a defect in tyrosine aminotransferase (reaction 1, Figure 30-12), and in neonatal tyrosinemia, due to lowered y>-hydroxyphenylpyruvate hydroxylase activity (reaction 2, Figure 30-12). Therapy employs a diet low in protein. 

Figure 20.22 Catabolism of phenylalanine and tyrosine. A indicates the lesion in classic phenylketonuria B indicates a tyrosinemia caused by tyrosine transaminase deficiency C indicates a tyrosinemia caused by p-hydroxyphenylpyruvate oxidase deficiency and the lesion in neonatal tyrosinemia D indicates alcaptonuria.

Additional errors of phenylalanine and tyrosine metabolism include tyrosinosis, or hereditary tyrosinemia, neonatal tyrosinemia, and alcaptonuria. In the first case, there is a probable defect in p-hydroxyphenylpyruvate oxidase. In neonatal tyrosinemia, the problem is transient and may be solved by the administration of ascorbic acid. Ascorbic acid is apparently a cofactor for p-hydroxy-phenylpyruvate oxidase. Alcaptonuria is a benign disorder in which homogen-tisic acid oxidase is inoperative and homogentisic acid is excreted in the urine. Air oxidizes the homogentisic acid to a pigment, giving urine a black color. This pigment also accumulates in the patient s tissues. 

The most common cause of an elevation of the serum phenylalanine level about 3 mg dl is the transient neonatal delay in the development of the tyrosine oxidizing system (transient neonatal tyrosinemia). This condition, while far more common in low-birth-weight and premature infants, does occur occasionally in full-term infants as weU. The elevation of phenylalanine is secondary to a block in the metabolism of tyrosine. Administration of 100 mg of ascorbic acid will reduce the tyrosine levels, but whether this is necessary is an area of some controversy (Cohn and Roth 1983). 

Jakobs C, Dorland L, Wikkerink B, Kok RM, de Jong AP, Wadman SK. Stable isotope dilution analysis of succinyiacetone using electron capture negative ion mass fragmentography an accurate approach to the pre- and neonatal diagnosis of hereditary tyrosinemia type I. CHn Chim Acta 1988 171 223-31. 

Neonatal screening Transaminases ( ) a-Fetoprotein (+) Prothrombine time ( ) Porphobilinogen synthase deficiency +) Succinylacetone (+) Tyrosinemia type I (tyr(P) 120-1300 pmol/l)... 

Schulze A, Frommhold D, Mayatepek E, Hoffmann GF (2000) A new approach in neonatal screening for hereditary tyrosinemia type 1. J Inher Metab Dis 23, Suppl 1 7... 

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