The
European Urea Cycle Disorder Group
The European UCDS
(Urea Cycle Disorders Study)
Urea cycle disorders (UCDs) are a group of inherited inborn errors of metabolism that interfere with the catabolism of protein within the human liver into urea. Ammonia is produced, a chemical that is highly toxic to the human body, and these disorders are associated with a high mortality and morbidity. There are eight disorders in total; six involve enzymes that directly form part of the urea cycle and a further two are mitochondrial membrane transporters involved in urea biosynthesis. Accurate incidence rates are difficult to determine but an extensive search of the medical literature suggests the following rates:
| Ornithine transcarbamylase (OTC) deficiency | 1:14.000 |
| Argininosuccinate synthetase (ASS) deficiency | 1:57.000 |
| Carbamylphosphate synthetase 1 (CPS1) deficiency | 1:62.000 |
| Argininosuccinate lyase (ASL) deficiency | 1:70.000 |
| Arginase1 (AR1) deficiency | 1:350.000 |
| Citrullinaemia type II or citrin deficiency | 1:21.000 in Japan |
| N-acetylglutamate synthase (NAGS) deficiency | very rare |
| Hyperornithinaemia-hyperammonaemia-homocitrullinuria (HHH) syndrome | very rare |
| Note: Citrullinaemia type II or citrin deficiency is quoted as 1:21000 in Japan but is considered to be very rare in other parts of the world. | |
The planned study will initially centre on three countries, France, Germany and the United Kingdom with the aim of expanding to include other European countries at a later date. Each country will have a principal centre and it is intended that patients will be referred within each country to this study centre. This will permit a series of standardised neurological and other tests to be performed by one group of staff, reducing the variability inherent in the use of multiple centres within a country. Geographical considerations in each country may preclude all the patients being seen in just one study centre so additional regional centres will be recruited into the study, as necessary. Studying the international literature, the clinical history of these disorders is poorly understood and the current study is designed to measure and record presenting signs and symptoms, and measure quality of life determinants and outcomes and compare these with the current best clinical practice in each country. The intention is that over a period of some years this work will identify predictive biomarkers for these disorders that will help in choosing an appropriate treatment regimen and assist in predicting the prognosis of the disease for each patient.
Currently there are no standardized treatment regimens across Europe for any of these disorders and thus determination of the outcome of different current treatment strategies is a major aim of the present study. It should be stressed that this is anticipated to be a continuing study with data collected over a number of years, identifying additional areas for future medical research. (2323 characters)
Our project will be made up of a series of Work Packages
WP1; The creation, administration and management of the research network.
WP2; Creation and continuing maintenance of a series of interlinked
databases (clinical, patient registry, mutational and/or enzymatic,
biochemical, nutritional, and neuropsychological).
WP3; Describes the biochemical, mutational and/or enzymatic analyses of
patient samples needed for confirmation of a clinical diagnosis
WP4: Awareness and publicity.
WP5; Education and training of medical staff.
WP6; Evaluation and validation of different therapies and other UCD-related
research programmes.
WP7; Coordinates the gradual extension of the number of participating centers
