1 results
29 - Tyrosinemia
- from SECTION IV - METABOLIC LIVER DISEASE
-
- By Grant A. Mitchell, M.D., Professor, Department of Pediatrics, CHU Sainte-Justine and Université de Montréal, Montréal, Québec, Canada, Pierre A. Russo, M.D., Professor of Pathology and Pediatrics, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, Josée Dubois, M.D., F.R.C.P., Professor of Radiology, Department of Radiology, CHU Sainte-Justine and Université de Montréal, Montréal, Québec, Canada, Fernando Alvarez, M.D., Professor of Pediatrics, Department of Pediatric Gastroenterology, CHU Sainte-Justine and Université de Montréal, Montréal, Québec, Canada
- Edited by Frederick J. Suchy, Mount Sinai School of Medicine, New York, Ronald J. Sokol, University of Colorado, Denver, William F. Balistreri, University of Cincinnati
-
- Book:
- Liver Disease in Children
- Published online:
- 18 December 2009
- Print publication:
- 07 May 2007, pp 694-713
-
- Chapter
- Export citation
-
Summary
Hepatorenal tyrosinemia is a fascinating inborn error of metabolism that can affect numerous organs, particularly the liver, kidneys, and peripheral nerves. The first report of a patient with elevated blood tyrosine was by Medes in 1932 [1]. Patients with a more typical clinical and biochemical picture of tyrosinemia were then described in the late 1950s [2–5]. Since then, more than 500 patients have been reported in the literature [6–8] or enrolled in the International NTBC [2-(2-nitro-4-trifluoromethyl benzoyl)-1,3-cyclohexanedione] Trial. Previously, almost all patients died in infancy and early childhood, and only isolated case reports described affected adults. In the 50 years since the description of tyrosinemia [3], the course of the disease has been improved successively by the introduction of diet therapy, neonatal screening, and hepatic transplantation. The advent of liver and kidney transplantation as a definitive treatment [7–11] revolutionized the outcome. Recently, the availability of NTBC, a chemical now designated as nitisinone and commercialized as Orfadin (Swedish Orphan International AB), has provided hope for a nonsurgical solution for some patients. On a fundamental level, tyrosinemia raises questions in hepatology, biochemical and population genetics, cell biology, oncology, and public health.
PATHOPHYSIOLOGY
Tyrosinemia is caused by a deficiency of fumarylacetoacetate hydrolase (FAH; enzyme [EC] 3.7.1.2), the last enzyme of tyrosine degradation (Figure 29.1A). The site of the primary metabolic block in tyrosinemia was elegantly deduced by Lindblad et al. in 1977 [12] and subsequently confirmed enzymatically by several investigators [13–15].