Hereditary tyrosinaemia type I: from basics to progress in treatment.
ABSTRACT Hereditary tyrosinaemia type I is the most common of the diseases caused by defects in tyrosine metabolism. The underlying genetic defect is a mutation in the gene for fumarylacetate hydrolase (FAH), and more than 30 different mutations in this gene have been identified. The main clinical consequences of this defect include hepatic involvement, with a high risk for liver cancer, and renal tubular dysfunction. Restriction of phenylalanine and tyrosine from the diet along with supportive measures can ameliorate the symptoms, but cure has so far been possible only with liver transplantation. Recent discovery of a pharmacological treatment with a peroral inhibitor of tyrosine catabolic pathway, 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), offers a new promising tool for the treatment of patients with hereditary tyrosinaemia type I. Mouse models of FAH deficiency have been successfully used in experimental gene therapy, and these studies indicate that future management of tyrosinaemia with a gene therapeutic approach may become feasible.
- SourceAvailable from: Sharon E Plon[Show abstract] [Hide abstract]
ABSTRACT: Mutations in genes that play fundamental roles in metabolic pathways have been found to also play a role in tumor development and susceptibility to cancer. At the same time, significant progress has been made in the treatment of patients with inborn errors of metabolism (IEM),(1) resulting in increased longevity and the unmasking of cancer predisposition, frequently hepatocellular carcinoma, in these conditions. These patients offer a potential opportunity to deepen our understanding of how intermediary metabolism impacts tumorigenesis. We provide an overview from the perspective of cancers in patients affected with IEM and discuss how dysregulation of these specific metabolic pathways might contribute to the mechanisms of cancer development and treatment.The American Journal of Human Genetics 04/2011; 88(4):402-21. · 11.20 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Western countries are finding health care costs to be a continuously increasing financial burden in excess of previous budgetary allocations. With current health care costs accounting for greater than 15% of the national expenditure, governments are seeking innovative cost-limiting strategies. Medical nutrition therapy (MNT) has proven to be an efficient cost minimising tool whilst concurrently ameliorating the patient's quality of life. In the MNT approach, the incorporation of foodomics technologies in medical foods has a pivotal role regarding quality, safety, nutrition and health. These MNT are defined as specially processed or formulated foods that are used for the dietary management of patients. Amongst the medical foods, low-protein/protein-free (LP/PF) foods have been shown to improve the physical manifestation of metabolic disorders in patients with amino acid or protein-related diseases, such as Phenylketonuria, Tyrosinaemia type I, as well as chronic kidney, and coeliac. Most of the cereal-based LP/PF foods currently marketed are a blend of refined or chemically-based food ingredients with unpalatable, frequently artificial flavours, having excessive sweetness to mask the chemical tasting ingredients (drug-like approach). However, the adoption of an alternative to convention, such as a food-like approach to developing medical foods, is a surprisingly complex process. This is specifically true when the technological aspects of LP/PF foods and, in particular, protein-free cereal foods are considered. The primary processing issues arise when trying to replace gluten in baked cereal products. This presents a significant technological challenge, as gluten is an essential structural network-building protein necessary for formulating high-quality baked goods. Additional considerations such as physical/chemical compatibility, product shelf life, appearance, and palatability determine the success and potential for commercialisation of these therapeutic foods. In this review, the suitable food technology strategies, in particular the foodomics research areas comprising genomics, proteomics, metabolomics and materiomics, for developing LP/PF cereal foods able to overcome the significant limitations of a food-like approach will be addressed.Food Research International 03/2013; · 3.01 Impact Factor
- American Journal of Human Genetics - AMER J HUM GENET. 01/2011; 63(1):31-33.