carbamoyl phosphate synthetase I deficiency disease

Carbamoyl phosphate synthetase I deficiency disease is a severe metabolic disorder that disrupts the urea cycle and results in the accumulation of toxic levels of ammonia in the body. It is caused by pathogenic variants in the CPS1 gene, which encodes an enzyme critical for converting ammonia to urea. Affected individuals often present during the neonatal period with severe hyperammonemia, although later-onset presentations with milder symptoms may also occur. Because precise prevalence estimates are not well established, the condition is understood to be very rare.

The clinical presentation commonly begins with lethargy and progresses to severe episodes of hyperammonemia, which can manifest as seizures, respiratory insufficiency, and hypotonia. Along with these acute metabolic crises, affected individuals may experience neurological challenges that impact developmental progress and, in some cases, cognitive functioning. Other features such as episodic symptoms of ammonia intoxication, hypoargininemia, and even stroke in a subset of patients highlight the varied nature of this disorder. Not all individuals experience all features, and severity varies considerably.

Carbamoyl phosphate synthetase I deficiency disease is caused by pathogenic variants in the CPS1 gene. The CPS1 gene codes for an enzyme essential in the urea cycle, responsible for converting ammonia into urea, thereby preventing toxic buildup. This condition is inherited in an autosomal recessive pattern, which means that an affected individual must inherit two abnormal copies of the CPS1 gene, one from each parent. Parents are typically unaffected carriers, and there is a one in four chance with each pregnancy for an affected child to be born.

Currently, management for carbamoyl phosphate synthetase I deficiency disease focuses on supportive care and symptom management. Treatment strategies are aimed at reducing blood ammonia levels through dietary management, medications to stabilize metabolism, and prompt intervention during episodes of hyperammonemia. As there are no FDA-approved treatments specifically for this condition, care is tailored by a multidisciplinary team to address the individual needs of the patient. Genetic counseling is recommended to help families understand the implications of this autosomal recessive condition and to explore available management options with their healthcare team.

The outlook for individuals with carbamoyl phosphate synthetase I deficiency disease varies considerably based on the severity of hyperammonemia and the timeliness of intervention. With current standards of care, many individuals may experience stabilization following initial crises, although ongoing challenges, particularly neurological, can persist. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with metabolic specialists and genetic counselors for additional support and guidance regarding long-term management.

Several clinical trials are currently investigating new treatment approaches for carbamoyl phosphate synthetase I deficiency disease. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.