Arginase Deficiency

Urea cycle disorders (UCD) are rare diseases in China that can cause high mortality and disability, requiring long-term management due to recurring symptoms. This multi-center, prospective, single-arm study aims to evaluate the safety and effectiveness of Glycerol Phenylbutyrate in Chinese children with UCD. The goal is to provide more treatment options and improve clinical care for these patients in China. The study plans a total observation period of five years for patients on long-term treatment with this medication. The study involves 40 children aged from birth to 18 years diagnosed with various types of UCD, including carbamoyl phosphate synthetase I deficiency and others. Participants will receive Glycerol Phenylbutyrate oral liquid, with dosing based on body surface area and divided into multiple daily doses taken with meals. The study includes scheduled clinic visits at 1 month and 3 months after enrollment, followed by visits every 6 months up to 5 years. During these visits, researchers collect data on adverse events, dosage changes, hyperammonemic crises, and blood ammonia levels. Participants will undergo regular assessments including blood tests for ammonia and biochemistry, growth measurements (height, weight, head circumference), and neurocognitive evaluations at specified intervals. The primary outcome is the mean blood ammonia level at 3 months after enrollment. Secondary outcomes include ammonia levels at multiple timepoints, frequency of crises, growth data, dosage adjustments, and various neurodevelopmental scores measured annually. This comprehensive follow-up aims to monitor safety, treatment effects, and overall development throughout the five-year period.

Researchers are investigating whether people with certain inherited ammonia metabolism disorders can successfully measure their ammonia levels daily at home. The study focuses on understanding participants' ability to regularly use a new ammonia measurement device and complete daily health monitoring. This research aims to improve management of conditions like urea cycle disorders and other metabolic diseases that affect ammonia processing in the body. Participants will use an investigational ammonia device that measures total ammonia from a single drop of blood using a reusable instrument and single-use cartridge. They will be asked to measure their ammonia levels daily, along with temperature, heart rate, and blood oxygen. The study includes two in-person clinic visits and an optional extension period, with monitoring lasting approximately 240 days, extendable by another 120 days. During the study, participants will complete daily surveys and record their health measurements to help researchers track adherence and gather data. The main outcome measured is the percentage of daily ammonia tests completed. Researchers will also analyze descriptive statistics and correlations over the study period to better understand home monitoring feasibility and patterns. Participants' involvement lasts around 8 months, with optional continued participation for an additional 4 months.

Urea cycle disorders (UCDs) are common inherited liver metabolism conditions. Improved diagnosis and treatments have increased survival rates, revealing some long-term liver complications like dysfunction and fibrosis in some patients. These liver issues vary depending on the specific metabolic defect causing the disorder. The study aims to better understand these complications by examining liver tissue samples from individuals diagnosed with any UCD. This research involves reviewing past medical records and prospectively collecting liver tissue samples from patients with confirmed UCD diagnoses. It includes individuals who have had or are planning to have liver biopsies or transplants. This observational study is conducted across multiple centers within the Urea Cycle Disorders Consortium, including Baylor College of Medicine and Children’s National Medical Center. Participants' liver samples will be evaluated for fibrosis, fat accumulation (steatosis), and glycogen buildup (hepatic glycogenosis). Researchers will analyze histopathology reports, biopsy slides, and tissue blocks to identify these outcomes. The study collects data retrospectively and prospectively, tracking histological changes to better understand liver complications in UCD. Participation involves no interventions and focuses on reviewing existing and new liver tissue findings until study completion in June 2026.

Urea cycle disorders (UCD) are rare inherited conditions that affect how the body processes protein, leading to dangerous ammonia buildup that can cause brain damage or death. This research aims to study a large group of individuals with different types of UCD to understand the natural course of the disease, how it progresses, treatments used, and patient outcomes over time. The study is observational and focuses on tracking biochemical status, growth, cognitive function, and treatment effects in participants. Participants will have an initial visit that includes medical and diet history, physical and neurological exams, psychological testing, and blood tests. Those with neonatal onset UCD will be assessed every 3 months until age 2, then every 6 months after that. Participants with late onset UCD will have evaluations every 6 months. Psychological testing occurs every 2 years and can last from 30 minutes to 3 hours depending on the tests. During the study, participants will undergo regular assessments lasting 2 to 3 hours at each visit. Researchers will monitor disease severity through various biomarkers and clinical indicators, evaluating the safety and effects of different treatments like alternate pathway therapy and transplantation. The study will continue longitudinally, allowing for long-term observation of participants' health and cognitive outcomes as they grow and receive care.

Urea cycle disorders (UCDs) are rare genetic conditions affecting how the body removes ammonia, a waste from protein breakdown. This research focuses on ornithine transcarbamylase deficiency (OTCD), the most common type, and other related disorders such as argininosuccinate synthetase deficiency (ASSD) and argininosuccinate lyase deficiency (ASLD). The study aims to understand brain changes and cognitive effects linked to these disorders by comparing brain chemical levels and structural abnormalities using advanced imaging and neuropsychological testing. The study includes three parts: a longitudinal study of OTCD, a recovery study after hyperammonemic episodes, and a longitudinal study of distal UCDs like ASSD and ASLD. Participants will undergo various brain imaging methods including standard MRI, functional MRI, diffusion tensor imaging, and magnetic resonance spectroscopy to assess brain chemistry and structure. Behavioral and cognitive tests will be performed alongside imaging during initial and follow-up visits. Participants will attend initial visits involving medical history reviews, neurological exams, and cognitive and motor testing over one to two days. They will undergo multiple imaging sessions while performing tasks during functional MRI. Researchers will measure changes in brain glutamine and myo-inositol levels and fractional anisotropy over two years, alongside behavioral outcomes. The study includes safety monitoring and aims to clarify brain damage progression in different UCD types.

Researchers are conducting a patient registry and natural history study called Coordination of Rare Diseases at Sanford (CoRDS) to support research on rare diseases. CoRDS is an international registry that connects patients with rare, undiagnosed, or uncommon diseases to researchers studying over 7,000 rare diseases. This program aims to help advance treatments and cures by facilitating easy collaboration between patients, advocacy groups, and researchers. It is based at Sanford Research in Sioux Falls, South Dakota, and is free for patients to join and for researchers to access. Participants provide contact, sociodemographic, and health information, which is entered into CoRDS and linked to a unique coded identifier. Examples of collected data include name, mailing address, phone number, email, date and place of birth, sex, gender, ethnicity, family history, and diagnosis-related information. De-identified information may be shared with approved researchers after review by an Institutional Review Board and expert panel. Some data may also be shared with other databases and patient advocacy groups, with protections to prevent misuse for research purposes. Participants are contacted yearly to confirm continued participation and to update their information. If a parent or legal guardian consents for a minor, the participant will be contacted at age 18 to provide their own consent. The primary goal is to accelerate research by connecting individuals interested in rare disease research with scientists over a long period of up to 100 years. There is no treatment given, as this is an observational registry study.

This research investigates brain injury biomarkers in patients with inherited hyperammonemic disorders and other metabolic conditions. High ammonia levels in the blood can harm the brain, causing swelling, blood vessel problems, intellectual disabilities, and in severe cases, coma or death. The study aims to understand the timing of brain injury markers during hyperammonemic episodes and to explore these markers in other metabolic diseases like Maple Syrup Urine Disease and Glutaric Acidemia. Participants include those diagnosed with specific urea cycle disorders, organic acidemias, fatty acid oxidation disorders, or hypoxic-ischemic encephalopathy. The study involves collecting and analyzing blood samples for biomarkers S100B, NSE, and UCHL1 during hospital stays and outpatient visits. These measurements will track biomarker changes alongside blood ammonia levels and neurological status. Patients will be enrolled during hospitalizations or preferably at outpatient visits, where leftover blood samples from routine tests are used. Biomarker levels will be measured sequentially during hospital stays until ammonia and mental status normalize, and again at follow-up outpatient visits to assess recovery. Researchers will monitor biomarker patterns over up to two years to better understand brain injury progression and recovery in these conditions.

Urea cycle disorders (UCDs) are dramatic congenital inherited metabolic disorders. There is no cure. Many novel therapeutic approaches are currently being developed, which hopefully will change the current situation. Testing the efficacy of such new therapies in patients is a challenge, because many clinical parameters are influenced by several disturbances and biochemical parameters are often not very specific. The measurement of ureagenesis is a tool to analyze the entire function of the urea cycle in a single test. This is more meaningful for the characterization of UCD patients than the analysis of single metabolites or enzymes. Therefore, the test will be important to evaluate current and future novel therapies. The term "ureagenesis" means "production of urea", which is the main task of the urea cycle. This total urea production can be measured with a "tracer" (in this case a stable ammonium chloride isotope). This tracer is non-radioactive and non-toxic. It is for example used as an unmarked substance in cough syrup, diuretic drugs and as food additive. Thus, the tracer does not pose a risk to the participant, especially since only a very low dose is applied. The investigators will analyze specific substances from the urea cycle (namely \[15N, 14N\] urea and several \[15N\] amino acids) that are produced during the test and compare them with results from healthy people. Venous and capillary blood will be sampled at 15 to 30 minutes intervals up to 2 hours after administration of the stable isotope tracer. The maximum test duration is 5 hours. This project is being carried out at one site, namely the University Children's Hospital in Zurich. This project is being carried out under Swiss law. The responsible Ethics Committee has reviewed and approved the study.