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.

Researchers are studying how the brain functions in people with urea cycle disorder UCD while they perform driving tasks of varying difficulty. This observational study compares brain activity during simulated driving between individuals with UCD and healthy volunteers, aiming to understand differences in thinking and attention. The study uses functional near-infrared spectroscopy fNIRS to measure brain oxygen levels in specific areas during these tasks. Participants will wear a soft cap equipped with fNIRS sensors that monitor oxygen changes in different brain regions such as the prefrontal, parietal, and occipital areas while they complete a driving simulation. The study includes both individuals diagnosed with UCD and healthy control participants matched by age and sex. All activities, including neurological exams, questionnaires about health and driving habits, and cognitive tests, will be conducted in one visit. Participants will have their medical history reviewed and complete simple memory and attention tests to assess cognitive skills. Brain oxygenation levels will be recorded during the driving task to evaluate brain function. The study measures changes in oxyhemoglobin, deoxyhemoglobin, and total hemoglobin concentrations in different brain regions in both groups. All study procedures, including assessments and simulator use, take place during a single day of enrollment.

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 Childrens 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.

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.

Researchers are conducting a Phase 12 open-label trial to study the safety, tolerability, and effectiveness of a single intravenous dose of LNP.UCD.ABE in five pediatric patients with severe infantile-onset urea cycle disorders UCDs. This trial targets children under 5 years old who have specific genetic variants in UCD-related genes that can be corrected by an adenine base editor ABE. Each participant will receive a personalized version of LNP.UCD.ABE, which is a gene editing therapy delivered via a lipid nanoparticle containing messenger RNA for the adenine base editor and guide RNA. Before treatment, each childs personalized drug will be developed and evaluated during a screening period lasting up to eight months. After a lead-in period to establish a stable diet, the child will receive a single intravenous infusion of the therapy and then be monitored. During the study, participants will be followed for 52 weeks after treatment to assess safety and tolerability. Researchers will perform various clinical evaluations, biochemical tests, and monitoring to measure the therapys effects. The main outcome is safety over 52 weeks, with secondary outcomes assessing clinical efficacy at 16 weeks. The total participation period may extend from screening through the follow-up phase lasting about one year.

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 serious inherited metabolic conditions without a cure. Researchers are developing new treatments but testing their effects is difficult because many clinical and biochemical factors affect measurements. This study aims to measure ureagenesis, the production of urea by the urea cycle, using a stable ammonium chloride isotope tracer to better assess urea cycle function in both healthy individuals and patients with UCD. Participants receive a non-radioactive, non-toxic stable isotope tracer, which is commonly used in medications and food additives at low doses. This tracer allows researchers to track total urea production in a single test. Blood samples are taken from veins and capillaries at intervals of 15 to 30 minutes for up to 2 hours after tracer administration, with a maximum test duration of 5 hours. During the study, researchers analyze specific substances related to the urea cycle in the blood and compare results between healthy participants and UCD patients. The main measurement is the rate of urea cycle activity both at baseline and after any interventions up to one year later. The study is conducted at one site under Swiss law with ethics committee approval, and involves healthy volunteers as well as patients with confirmed UCD.