Longitudinal Study of Urea Cycle Disorders

Children'S Research Institute, Washington DC

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Abstract

Urea cycle disorders (UCD) are a group of 8 rare but devastating inborn errors of metabolism that carry a high mortality and morbidity from the newborn period through adulthood. UCD include deficiencies in any of the six enzymes and two membrane transporters involved in urea biosynthesis: N-acetylglutamate synthase (NAGS); Carbamyl phosphate synthase I (CPSI) deficiency; Ornithine transcarbamylase deficiency (OTCD); Argininosuccinate synthase (AS) deficiency (Citrullinemia); Argininosuccinate lyase (AL) deficiency (Argininosuccinic aciduria); Arginase (ARG) deficiency (Argininemia); Hyperornithinemia, hyperammonemia, homocitrullinuria (HHH) syndrome; and Citrullinemia type II. The purpose of the longitudinal project is to perform a long-term follow-up study of a large group of patients with UCD. We will assess biochemical status, nutrition and cognitive function over time. We will evaluate morbidity and mortality of the two most commonly used forms of treatment for UCD, alternate pathway therapy and liver transplantation. We will also seek to identify biochemical parameters (biomarkers) that may predict future metabolic imbalances so that they can be corrected before clinical symptoms develop. The overall goal of this study is to improve treatment and outcome of this devastating group of disorders. The specific aims are to address the following questions: a. In the longitudinal cohort, what is the prevalence of specific morbid indicators of disease severity, including hyperammonemia, developmental disabilities, and various long-term renal and hepatic abnormalities? b.What is the relationship between various biomarkers and disease severity and progression? c.What is the safety and efficacy of currently used and new UCD therapies?