Tyrosinaemia type

McKiernan PJ, Nitisinone in the treatment of hereditary tyrosinaemia type 1, Drugs 66 743-750, 2006. 

Tyrosinaemia type II is caused by reduced activity of tyrosine aminotransferase, resulting in a greater concentration of tyrosine in the serum. This may develop into an independent congenital-hereditary clinical picture or physiological hypertyrosinaemia, which occurs in about 10% of newborns as a neonatal-transitory event. 

Lindstedt, S., Holme, E., Lock, E.A., Hjalmarson, O., Strandvik, B. Treatment of hereditary tyrosinaemia type I by inhibition of 4-hydro-xyphenylpyruvate dioxygenase. Lancet 1992 340 813—817... 

Macvlcar, D., Dicks-Mireaux, C., Leonard, J.V., Wight, D.GJ) Hepatic imaging with computed tomography of chronic tyrosinaemia type 1. Brit. X Radiol. 1990 63 605-608... 

Genetic mechanisms A genetic disposition is suspected in HCC, as in other malignant tumours. Some 22% of patients suffering from HCC had other organ tumours as well. (135) Several hereditary metabolic diseases, with or without cirrhosis, may increase the risk of HCC considerably. These include tyrosinaemia (type I), glycogenosis (type I), alphai-antitrypsin deficiency, galactos-aemia, porphyria cutanea tarda, acute intermittent porphyria and idiopathic haemochromatosis. Patients... 

Baumann, U., Rodeck, B. Liver transplantation in tyrosinaemia type 1 (in German). Mschr. Kinderheilk. 2004 152 1102-1106... 

Hereditary tyrosinaemia type I is a rare genetic disease caused by mutations in the gene for the enzyme fumaryl-acetoacetase, which results in severe liver failure and early death. 

Hereditary tyrosinaemia type II is caused by a deficiency of tyrosine aminotransferase, leading to eye lesions, skin lesions and neurological complications. The aim of dietary management is to prevent the accumulation of tyrosine and phenylalanine by a low-protein diet. The protein requirements are met by supplementing the diet with a tyrosine- and phenylalanine-free amino acid mixture. 

Holme E, Lindstedt S (1998) Tyrosinaemia type I and NTBC (2-(2-nitro-4-trifluoro-methylbenzoyl)-l,3-cyclohexanedione J Inher Metab Dis 21 507-517 Huhn R, Stoermer H, Klingele B, Bausch E, Fois A, Farnetani M, Di Rocco M, Boue J, Kirk JM, Coleman R, Scherer G (1998) Novel and recurrent tyrosine aminotransferase gene mutations in tyrosinemia type II. Hum Genet Mar 102(3) 305-313... 

Fig. 16.13 Chromatograms of organic acids extracted using DEAE-Sephadex (upper) and DEAE-Sephadex with solvent re-extraction (lower) from an infant with hereditary tyrosinaemia type I. Separated as their ethoxime and trimethylsilyl derivatives on 10 per cent OV-101 on HP Chromosorb W (80-100 mesh) using temperature programming from 110°C to 285°C at 4°C min with a 5 min initial isothermal delay. Peak identifications are 1, lactate 2, pyruvate 3, sulphate 4, phosphate 5, succinate 6, tetronates 7, aconitate plus homovanillate 8, hippurate 9, citrate plus isocitrate 10, 4-hydroxy-phenyl-lactate 11, 4-hydroxyphenylpyruvate (ethoxime) 12, vanil-lactate 13, 4-hydroxyphenylpyruvate (tri-TMS) 14, urate 15, n-tetracosane (standard) 16, n-hexacosane (standard). (The horizontal axes represent the time elapsed in minutes from sample injection.) The predominance of 4-hydroxyphenyl-lactate and the absence of 4-hydroxyphenylacetate is notable. There is no evidence for the metabolites observed by Lindblad etfl/. (1977) (see Fig. 16.14).

Fig. 16.16 Inherited metabolic diseases associated with hepatorenal dysfunction and tyrosyluria and close similarities to hereditary tyrosinaemia type I. (From Chalmers, 1974)...

Michals, K., Matalon, R. and Wang, P.W.K. (1978), Dietary treatment of tyrosinaemia type I. Importance of methionine restriction. J. Am. Dietetic Assoc., 73,507. 

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