neonatal-onset type II citrullinemia

Neonatal-onset type II citrullinemia, also known as neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), is a rare and serious liver disorder that affects newborns. The condition is characterized by the accumulation of ammonia and other toxic substances in the blood, which can lead to severe complications.

Symptoms:

• Neonatal hyperammonemic encephalopathy: This is a life-threatening condition that occurs when high levels of ammonia build up in the blood, causing lethargy, seizures, and coma.
• Hepatic dysfunction: The liver becomes damaged, leading to poor growth, failure to thrive, and other complications.
• Steatosis: The liver becomes fatty, which can lead to further damage and complications.

Causes:

Neonatal-onset type II citrullinemia is caused by a mutation in the SLC25A13 gene, which codes for the citrin protein. This protein plays a crucial role in the transport of ammonia out of the liver cells. When this protein is defective, ammonia builds up in the blood, leading to the symptoms described above.

Description:

The condition is often characterized by:

• Poor growth: Infants with NICCD may experience poor growth and development.
• Failure to thrive: Children with NICCD may experience failure to thrive, which can lead to further complications.
• Hepatic fibrosis: Scarring of the liver tissue can occur, leading to further damage and complications.

References:

• [3] The signs and symptoms appear during adulthood and are triggered by certain medications, infections, surgery, and alcohol intake.
• [5] Citrullinemia is an inherited disorder that causes ammonia and other toxic substances to accumulate in the blood.
• [13] This liver condition is also known as neonatal-onset type II citrullinemia. NICCD blocks the flow of bile (a digestive fluid produced by the liver) and prevents the body from processing certain nutrients properly.
• [15] Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is a liver condition that blocks the flow of bile and prevents the body from processing certain nutrients properly.

Neonatal-onset type II citrullinemia is a rare genetic disorder that affects the nervous system and liver in newborns. The symptoms of this condition can be severe and life-threatening if not treated promptly.

Common Symptoms:

• Severe cholestasis (reduced bile flow)
• Steatosis (fatty liver)
• Hypoglycemia (low blood sugar)
• Lethargy
• Seizures
• Coma

These symptoms can appear within the first few days of life and are often accompanied by a history of low birth weight and growth restriction.

Other Possible Symptoms:

• Transient intrahepatic cholestasis
• Abnormal behaviors (such as aggression, irritability)
• Confusion
• Restlessness
• Memory loss

It's worth noting that most patients with neonatal-onset type II citrullinemia show spontaneous improvement by 1 year of age. However, some may have a progressive course with continued failure to thrive and other complications.

References: [4] [5] [6]

Diagnosing Neonatal-Onset Type II Citrullinemia

Neonatal-onset type II citrullinemia is a rare genetic disorder that affects the body's ability to break down amino acids. Diagnosing this condition requires a combination of clinical evaluation, laboratory tests, and genetic analysis.

• Newborn Screening: The first step in diagnosing neonatal-onset type II citrullinemia is newborn screening, which involves measuring plasma ammonia levels and other biochemical markers [1].
• Additional Testing: If the newborn screening result indicates an out-of-range value for citrullinemia (CIT II), additional testing will be arranged to confirm the diagnosis. This may include blood tests, urine analysis, and genetic testing [15].

Diagnostic Tests

The following diagnostic tests are used to confirm a diagnosis of neonatal-onset type II citrullinemia:

• Blood Tests: Blood tests can measure the levels of certain amino acids, such as arginine and ornithine, which are often elevated in this condition.
• Urine Analysis: Urine analysis may reveal abnormal levels of certain compounds, such as citrulline and arginosuccinate.
• Genetic Testing: Genetic testing can identify mutations in the SLC25A13 gene, which is responsible for encoding a mitochondrial transporter involved in amino acid metabolism.

References

[1] Obtaining plasma ammonia level measurement when clinical signs and symptoms are suggestive of hyperammonemia, especially in the newborn. (Context #1) [15] If your baby’s newborn screening result for citrullinemia (CIT II) was out of the normal range, your baby’s doctor or the state screening program will contact you to arrange for your baby to have additional testing. (Context #15)

Treatment Overview

Neonatal-onset type II citrullinemia, also known as citrin deficiency, is a rare metabolic disorder caused by mutations in the SLC25A13 gene. The mainstay treatment for this condition involves nutritional therapy in early infancy using a

Neonatal-onset type II citrullinemia, also known as citrin deficiency, can be challenging to diagnose due to its similarity with other liver conditions. The differential diagnosis for this condition includes:

• Biliary atresia: A congenital disorder where the bile ducts are absent or blocked, leading to liver damage and jaundice.
• Choledochal cyst: A rare congenital anomaly where the bile duct is dilated, causing obstruction of bile flow and potentially leading to liver damage.
• Neonatal hepatitis syndrome: A condition characterized by inflammation of the liver in newborns, which can be caused by various factors such as infection, metabolic disorders, or genetic conditions.

In terms of metabolic differential diagnoses, citrin deficiency should also be considered alongside:

• Alpha1-antitrypsin deficiency: A genetic disorder that affects the production of a protein essential for protecting the lungs and liver from damage.
• Other metabolic disorders: Such as argininosuccinic aciduria, which is caused by a defect in the urea cycle.

It's essential to note that citrin deficiency can manifest differently depending on the age at presentation. In newborns, it may present as neonatal intrahepatic cholestasis (NICCD), while in older children and adults, it can lead to failure to thrive and dyslipidemia (FTTDCD) or recurrent hyperammonemia with neuropsychiatric symptoms (CTLN2), respectively.

A comprehensive diagnostic workup, including genetic testing, liver function tests, and imaging studies, is necessary to accurately diagnose neonatal-onset type II citrullinemia and rule out other differential diagnoses.