What is Carbamoylphosphate Synthetase I Deficiency?

Carbamoylphosphate synthetase I (CPS1) deficiency belongs to a group of disorders called urea cycle disorders. Individuals with CPS1 deficiency are missing an important liver enzyme. This leads to high ammonia levels in the blood (hyperammonemia), which can be harmful especially to the brain.

Most affected individuals will show symptoms within the first few days of life (neonatal-onset form), which may include unusual sleepiness, a poorly regulated breathing rate or body temperature, unwillingness to feed, vomiting after feeding, unusual body movements, seizures, or coma. Affected children who survive the newborn period may experience recurrence of these symptoms if diet is not carefully managed or if they experience infections or other stressors. They may also have delayed development and intellectual disability.

Less commonly, people with CPS1 deficiency, have moderate or mild severe symptoms that appear later during childhood or adulthood (late-onset form). Patients with the milder form of CPSI deficiency may still experience hyperammonemic coma and life-threatening complications.

How common is Carbamoylphosphate Synthetase I Deficiency?

The exact incidence of CPS1 deficiency is unknown, but is estimated to occur in approximately 1 in 1,300,000 infants born in the USA. Slightly higher incidences have been reported in less ethnically-diverse countries, such as Finland (1 in 539,000) and Japan (1 in 800,000).

How is Carbamoylphosphate Synthetase I Deficiency treated?

There currently is no cure for CPS1 deficiency. The treatment consists of dietary management to limit ammonia production along with medications and supplements that provide alternative pathways for the removal of ammonia from the bloodstream. Maintaining this special diet is needed to make sure that the individual gets enough calories and essential amino acids. Routine blood tests are needed to monitor the disorder and manage treatment. In some cases, transplants have been effective in reversing the symptoms.

What is the prognosis for a person with Carbamoylphosphate Synthetase I Deficiency?

CPS1 deficiency is the most severe of the urea cycle disorders. Outcomes vary, and depend on age at diagnosis and how closely the treatment plan and diet are followed. Some states screen all infants for this disease at birth. Infants who are diagnosed in the first week of life and are put on a diet immediately may reach normal brain function. Even with treatment, some individuals will experience hyperammonemic episodes leading to permanent intellectual disability and death. Without treatment, CPS1 deficiency results in death.

Other names for
carbamoylphosphate synthetase I deficiency

  • Carbamoyl-phosphate synthase 1, mitochondrial
  • Carbamoyl-phosphate synthetase I
  • Carbamoylphosphate synthetase I
  • Congenital hyperammonemia, type I


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