What Is Citrullinemia Type 1?

Citrullinemia type I is an inherited condition in which ammonia and other toxic substances build up in the blood, causing life-threatening complications shortly after birth. It is caused by mutations in the ASS1 gene. Citrullinemia type I belongs to a group of diseases known as urea cycle disorders. When the body consumes protein, it also produces excess nitrogen. Under normal circumstances, the body converts that nitrogen to urea, which is then excreted in the urine. People with citrullinemia type I are deficient in an enzyme known as argininosuccinate synthase, which is needed for this vital process, leading to a buildup of ammonia and other urea cycle byproducts in the body. The excess ammonia is harmful to the nervous system, causing many of the disease's symptoms.

Infants with citrullinemia type I appear normal at birth. However, within the first week of life most will become lethargic and display poor feeding, vomiting, and seizures that often lead to unconsciousness, stroke, increased pressure around the brain, and death if untreated.

A milder form of type I citrullinemia may develop later in childhood or adulthood, but this form of the disease is less common. This later-onset form is associated with intense headaches, partial loss of vision, problems with balance and muscle coordination (ataxia), episodes of elevated ammonia that are similar to the classic form, and lethargy. Women with the later-onset form may have an onset of severe symptoms during pregnancy or postpartum.

How Common Is Citrullinemia Type 1?

Scientists estimate that 1 in 57,000 births are affected by citrullinemia type I.

How Is Citrullinemia Type 1 Treated?

The goals of treatment for citrullinemia type I are to regulate the amount of ammonia in the blood. Physicians adhere to certain protocols to control the body's ammonia levels. These protocols use medication, dialysis, and a specifically prescribed diet. Children with citrullinemia will need to be monitored closely by a physician specializing in metabolic disorders. Physicians will also monitor and attempt to relieve any excess of pressure around the brain.

Lifelong management involves strict dietary management in addition to oral administration of sodium phenylbutyrate or glycerol phenylbutyrate and L-carnitine to prevent systemic hypocarnitinemia. Liver transplantation may be warranted.

What Is the Prognosis for a Person with Citrullinemia Type 1?

The prognosis for a child with citrullinemia type I is not well established. Without treatment, the longest-known survival was 17 days. With treatment, these children can survive for an unknown period of time, but they will have significant mental and neurological impairment.

Initial neurologic findings associated with the milder, late-onset form may be more subtle than those seen in the acute neonatal form because of the older age of affected individuals.


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  • OMIM: Online Mendelian Inheritance in Man, OMIM [603470], 2016, https://www.omim.org/entry/603470
  • Quinonez et al., 2016, https://www.ncbi.nlm.nih.gov/books/NBK1458/