Carbamoyl phosphate synthetase 1 deficiency (CPS1D) is a hereditary disorder defined by the complete or partial lack of the carbamoyl phosphate synthetase (CPS) enzyme. The CPS enzyme aids in the breakdown and removal of nitrogen from the body to aid in preventing the formation of ammonia in the blood. Symptoms of CPSID, caused by the accumulation of ammonia, include the refusal of a newborn child to eat, lethargy, lack of appetite, vomiting, and irritability. Newborns could also have subsequent seizures, respiratory distress, and atypical movements of their body. Ultimately, the liver and brain can be damaged.
CPS1D is recognized in one in 150,000 to 200,000 newborns. Understandably, CPS1D is more severe when there is a complete lack of the CPS enzyme. With milder forms of the disease, symptoms may not show up until later in the child's life.
Breakthrough Therapy
Baby KJ was two days old when he became more lethargic and stopped eating. After tests, it was noted that his blood ammonia level was elevated, and KJ was transferred to Children's Hospital of Philadelphia (CHOP). After further genetic testing, it was confirmed he had CPS1D.
A research team from CHOP and the Perelman School of Medicine at the University of Pennsylvania, supported by the National Institutes of Health, developed a customized gene therapy for baby KJ’s CPS1D. By utilizing the gene editing platform CRISPR (clustered regularly interspaced short palindromic repeats), the team was able to repair the specific gene in his liver cells that caused the deficiency. On February 25, 2025, baby KJ became the first person to receive personalized gene therapy. KJ has received two more infusions of the therapy. Since then, he has been growing and thriving with no severe side effects. Although the long-term effects are unknown, doctors are hopeful that this personalized gene therapy will endure.
Article written by Stacy Schumacher, RN, BSN, CMCN, Managed Care Specialist. The following sources were used as reference material for this article:
https://rarediseases.org/rare-diseases/carbamoyl-phosphate-synthetase-i-deficiency/