classic citrullinemia

Classic Citrullinemia Description

Classic citrullinemia, also known as citrullinemia type I (CTLN1), is a rare autosomal recessive genetic disorder that affects the body's ability to remove ammonia properly. This condition is characterized by the accumulation of toxic substances, including ammonia, in the blood.

Key Features:

• Progressive Lethargy: Affected babies typically appear normal at birth but experience a progressive lack of energy (lethargy) as ammonia builds up.
• Poor Feeding and Vomiting: Infants with classic citrullinemia often exhibit poor feeding habits and vomiting due to the toxic effects of ammonia on the digestive system.
• Elevated Serum Citrulline: The condition is marked by elevated concentrations of serum citrulline, a key indicator of citrullinemia.

Forms of Citrullinemia:

There are two main forms of citrullinemia:

1. Classic Form: This is the more severe form, typically seen in babies.
2. Mild Form: This form is first seen later in childhood or adulthood and is less severe than the classic form.

Inheritance Pattern:

Citrullinemia type I (CTLN1) is an autosomal recessive disorder, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition.

Classic Citrullinemia Signs and Symptoms

Citrullinemia, a rare genetic disorder, can manifest in two forms: classic and later-onset. The classic form is more severe and typically presents within the first few days of life.

• Excessive sleepiness: Infants with classic citrullinemia often experience excessive sleepiness or lethargy [6].
• Poor appetite: Babies may show poor appetite, which can lead to vomiting [3][9].
• Vomiting: Vomiting is a common symptom in infants with classic citrullinemia [3][9].
• Increased intracranial pressure: Infants may exhibit signs of increased intracranial pressure, such as progressive lethargy and refusal to eat [2].

If left untreated, high ammonia levels can cause more severe complications, including:

• Hypotonia: Weakness or floppiness in the muscles
• Breathing problems: Respiratory difficulties due to muscle weakness
• Seizures: Abnormal electrical activity in the brain leading to seizures
• Swelling of the brain: Increased intracranial pressure can cause swelling of the brain

Early treatment is essential to prevent these complications and ensure a better outcome for affected individuals.

Diagnostic Tests for Classic Citrullinemia

Classic citrullinemia, also known as citrullinemia type I (CTLN1), is a rare autosomal recessive genetic disorder that can be diagnosed through various diagnostic tests. Here are some of the key tests used to diagnose classic citrullinemia:

• Newborn Screening: Newborn screening programs can detect high levels of

Treatment Options for Classic Citrullinemia

Classic citrullinemia, also known as citrullinemia type I (CTLN1), is a rare genetic disorder that requires long-term management. The primary goal of treatment is to remove excess ammonia from the body and prevent complications.

• Medications: Medications are necessary to remove excess ammonia from the body. Ammonia scavenger drugs, such as sodium benzoate or phenylacetate, can be used to reduce ammonia levels in the blood [2][3].
• Dialysis: In severe cases, dialysis may be required to remove ammonia from the blood [1].
• L-Arginine Supplementation: L-arginine is an essential amino acid that must be replenished through supplementation. A higher dose of L-arginine is required in the management of citrullinemia [5][6].
• Protein-Restricted Diet: A protein-restricted diet is necessary to prevent excessive ammonia production in the body [4][6]. This involves limiting dietary intake of protein-rich foods.
• Long-term Treatment: Long-term treatment consists of a combination of these therapies, including a protein-restricted diet, ammonia scavenger drugs, L-arginine supplementation, and aggressive intervention for recurrent bouts of hyperammonemia [7].

Switching Treatment Options

Studies have shown that switching treatment options can be beneficial in managing citrullinemia. For example, one study found that switching from arginine monotherapy to combined treatment resulted in improved outcomes [8]. Another study found that switching from citrulline monotherapy to combined treatment also led to better results [9].

References

[1] May 1, 2017 — Citrullinemia is an inherited disorder that causes ammonia and other toxic substances to accumulate in the blood.

[2] by N Brunetti-Pierri · 2012 · Cited by 15 — Citrullinemia is a urea cycle defect requiring long-term care with nutritional and pharmacological management. Despite treatment, morbidity ...

[3] May 14, 2024 — Citrullinemia type I (CTLN1) or classic citrullinemia is the disease caused by a deficiency in the enzyme arginosuccinate synthase (ASS1) deficiency.

[4] by FHMD

Understanding Differential Diagnosis in Classic Citrullinemia

Classic citrullinemia, also known as citrullinemia type I (CTLN1), is a rare autosomal recessive genetic disorder caused by a deficiency in the enzyme arginosuccinate synthase (ASS1). The differential diagnosis of this condition involves identifying other possible causes of elevated serum and urine citrulline levels.

Key Considerations

• Neonatal acute form: This is the classic form of citrullinemia, characterized by markedly elevated plasma citrulline levels. Diagnosis is established by enzymatic or mutation analysis.
• Late-onset form: A milder form of citrullinemia that presents with neuropsychiatric symptoms and elevated serum citrulline concentrations.

Differential Diagnoses

• Citrullinemia type II (CTLN2): Another rare autosomal recessive disorder caused by a deficiency in the enzyme argininosuccinate lyase.
• Argininosuccinic aciduria: A urea cycle disorder characterized by elevated levels of argininosuccinic acid and citrulline in the urine.

Clinical Presentation

Classic citrullinemia typically presents with symptoms such as:

• Neonatal acute form: Markedly elevated plasma citrulline levels, ammonia intoxication, and severe neurological symptoms.
• Late-onset form: Neuropsychiatric symptoms, developmental delays, and seizures.

Diagnostic Approach

The diagnosis of classic citrullinemia is established by enzymatic or mutation analysis. Long-term treatment involves a combination of dietary restrictions, medication, and supportive care to manage symptoms and prevent complications.

References

• [3] Citrullinemia type I (CTLN1) or classic citrullinemia is the disease caused by a deficiency in the enzyme arginosuccinate synthase (ASS1) deficiency.
• [5] Citrullinemia type I (CTLN1) presents as a spectrum that includes a neonatal acute form (the "classic" form), a milder late-onset form (the "non-classic" form),
• [7] The classic form of citrullinemia, an autosomal recess