Citrullinemia

Citrulline

Citrullinemia is a rare genetic disorder that results from an enzyme deficiency, leading to an accumulation of citrulline and other toxic substances in the blood and urine. This condition is part of a group of disorders known as urea cycle disorders, which affect the body's ability to remove ammonia from the bloodstream. Ammonia is a toxic byproduct of protein metabolism that, in healthy individuals, is converted into urea and excreted in the urine. Citrullinemia is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the defective gene, one from each parent, to be affected.

Types of Citrullinemia

Citrullinemia is classified into two main types, each caused by mutations in different genes:

Type I Citrullinemia

Type I Citrullinemia, also known as Classic Citrullinemia or Citrullinemia Type I (CTLN1), is caused by mutations in the ASS1 gene, which encodes the enzyme argininosuccinate synthetase. This enzyme plays a crucial role in the urea cycle. The deficiency leads to a buildup of ammonia and citrulline in the blood, causing various symptoms. It is the more severe form of the disease and typically presents in the newborn period or early infancy.

Type II Citrullinemia

Type II Citrullinemia, or Citrullinemia Type II (CTLN2), is caused by mutations in the SLC25A13 gene, which encodes the mitochondrial aspartate/glutamate carrier. This form of the disease is also known as Adult-onset Citrullinemia and is characterized by the onset of symptoms later in life, often in adulthood. CTLN2 is associated with a different set of symptoms and has a somewhat different treatment approach compared to CTLN1.

Symptoms

The symptoms of Citrullinemia vary depending on the type but may include:

• Poor feeding
• Vomiting
• Lethargy
• Seizures
• Hypotonia (reduced muscle tone)
• Intellectual disability
• Hepatic encephalopathy in severe cases

Type II Citrullinemia may also present with symptoms related to chronic liver disease, such as jaundice, confusion, and memory loss.

Diagnosis

Diagnosis of Citrullinemia involves a combination of clinical evaluation, laboratory testing, and genetic testing. Elevated levels of citrulline in the blood and urine, along with high ammonia levels, can suggest the diagnosis. Genetic testing can confirm the specific type of Citrullinemia by identifying mutations in the ASS1 or SLC25A13 genes.

Treatment

Treatment for Citrullinemia aims to manage symptoms and prevent the buildup of ammonia in the blood. Dietary management to restrict protein intake is often necessary, along with the use of medications that help to remove ammonia from the body. In some cases, especially for Type I Citrullinemia, liver transplantation may be considered as a treatment option.

Prognosis

The prognosis for individuals with Citrullinemia varies. With early diagnosis and appropriate treatment, many individuals can lead relatively normal lives. However, the condition can be life-threatening, especially if not properly managed or if treatment is delayed.