argininosuccinic aciduria

What is Argininosuccinic Aciduria?

Argininosuccinic aciduria, also known as ASA, is a rare genetic disorder that affects the body's ability to remove nitrogen waste products. It is characterized by a deficiency or lack of the enzyme argininosuccinate lyase (ASL), which plays a crucial role in the breakdown and removal of nitrogen from the body through the urea cycle.

Key Features:

• Inherited disorder: Argininosuccinic aciduria is an inherited condition, meaning it is passed down from parents to their children.
• Urea cycle disorder: The disorder affects the urea cycle, a series of biochemical reactions that occur in the body to break down and remove excess nitrogen waste products.
• Enzyme deficiency: The lack or deficiency of the enzyme argininosuccinate lyase (ASL) is responsible for the condition.

Symptoms:

• Ammonia accumulation: Ammonia, a toxic chemical, accumulates in the blood due to the body's inability to remove nitrogen waste products.
• Neonatal-onset form: The severe neonatal-onset form of ASA can manifest with symptoms such as vomiting, hypothermia, lethargy, and poor feeding in the first few days of life.
• Late-onset forms: Late-onset forms of ASA can present with a range of symptoms, including neurological problems and developmental delays.

Prevalence:

• Rare genetic disorder: Argininosuccinic aciduria is considered a rare genetic disorder, with an estimated prevalence at birth ranging from 1/70,000 to 218,000 worldwide.

The information provided above is based on the following search results:

[4] [5] [6] [8] [9] [11] [12] [13]

Signs and Symptoms of Argininosuccinic Aciduria

Argininosuccinic aciduria, a rare inherited metabolic disorder, can manifest in various ways, depending on the severity and specific symptoms. Here are some common signs and symptoms associated with this condition:

• Poor feeding: Infants with argininosuccinic aciduria may show poor appetite or refusal to feed.
• Vomiting: Vomiting is a common symptom, especially in the first few days of life.
• Floppiness: Babies with argininosuccinic aciduria may appear lethargic or floppy due to excessive sleepiness.
• Rapid breathing: Respiratory problems can occur, leading to rapid breathing rates.
• Dehydration: Dehydration (lack of body fluids) is a possible symptom, especially in severe cases.

In more severe forms of the disorder, which are characterized by a complete or near-complete lack of the ASL enzyme, symptoms may include:

• Neonatal period complications: The nervous system is particularly sensitive to excess ammonia, leading to neurological problems and other signs and symptoms.
• Life-threatening problems: In rare cases, argininosuccinic aciduria can cause life-threatening complications if left untreated.

It's essential to note that the severity and specific symptoms of argininosuccinic aciduria vary from person to person. Early diagnosis and treatment are crucial in managing this condition effectively.

References:

• [1] Signs & Symptoms. The severity and specific symptoms of argininosuccinic aciduria varies from one person to another.
• [2] Argininosuccinic aciduria is an inherited disorder that causes ammonia to accumulate in the blood.
• [6] Signs and symptoms include: Poor feeding; Vomiting; Floppiness; Excessive sleepiness; Rapid breathing; Dehydration (lack of body fluids)
• [8] Signs of ASA in babies include poor appetite, sleeping longer or more often, tiredness, irritability, vomiting, trouble breathing, seizures (epilepsy), ...
• [13] Argininosuccinic aciduria – also known as argininosuccinase deficiency and argininocuccinate lyase deficiency (ALD) – is an inherited disorder that causes ammonia to accumulate in the blood.

Diagnostic Tests for Argininosuccinic Aciduria

Argininosuccinic aciduria, a rare genetic disorder, can be diagnosed through various specialized tests. The following diagnostic tests are commonly used to confirm the condition:

• Blood tests: Blood tests may reveal excessive amounts of ammonia in the blood, which is a key criterion for diagnosing urea cycle disorders, including argininosuccinic aciduria [1].
• Plasma amino acid analysis: This test reveals elevated levels of argininosuccinic acid and citrulline in the plasma, indicating the presence of the disorder [13].
• Urine amino and organic acids analysis: High levels of orotic acid in the urine may indicate argininosuccinic aciduria [4].
• ASL enzyme testing: This test measures the activity of the enzyme argininosuccinate lyase (ASL), which is deficient in individuals with argininosuccinic aciduria [6].
• Molecular genetic testing: Genetic testing confirms the diagnosis by identifying mutations in the ASL gene responsible for encoding the enzyme argininosuccinate lyase [12].

These diagnostic tests are typically performed after a positive newborn screening test or when symptoms of the disorder become apparent. A detailed patient/family history and clinical evaluation also play a crucial role in diagnosing argininosuccinic aciduria.

References:

[1] Blood tests may reveal excessive amounts of ammonia in the blood, which is a key criterion for diagnosing urea cycle disorders, including argininosuccinic aciduria. [4] High levels of orotic acid in the urine may indicate argininosuccinic aciduria. [6] ASL enzyme testing measures the activity of the enzyme argininosuccinate lyase (ASL), which is deficient in individuals with argininosuccinic aciduria. [12] Genetic testing confirms the diagnosis by identifying mutations in the ASL gene responsible for encoding the enzyme argininosuccinate lyase. [13] Plasma amino acid analysis reveals elevated levels of argininosuccinic acid and citrulline in the plasma, indicating the presence of the disorder.

The treatment of argininosuccinic aciduria (ASA) involves a combination of dietary management and medications to manage the condition.

Medications

• Arginine supplementation: Arginine is an amino acid that plays a crucial role in the urea cycle. Supplementing with arginine can help reduce ammonia levels in the blood [3][5].
• Nitrogen-scavenging therapy: This type of therapy uses medications such as benzoate or phenylbutyrate to remove excess nitrogen from the body [3][9].
• Nitrates: Nitrates, such as nitric oxide, can be used to reduce ammonia levels in the blood and improve metabolic stability [8].

Dietary Management

• Low-protein diet: A low-protein diet is often recommended to help manage ASA. This type of diet helps reduce the amount of nitrogen that needs to be excreted by the body [5][15].
• Arginine-rich diet: In some cases, a diet rich in arginine may be recommended to help supplement the body's natural production of this amino acid [3].

Other Therapies

• Nitric-oxide supplementation: Nitric oxide has been shown to have therapeutic benefits for individuals with ASA, particularly in reducing long-term complications such as neurocognitive impairment and hepatic disease [4].
• Gene therapy: Researchers are exploring the use of gene therapy to treat ASA by replacing or repairing the defective ASL gene [6].

It's essential to note that each individual with ASA may require a tailored treatment plan, taking into account their specific needs and medical history. A healthcare professional should be consulted for personalized advice on managing ASA.

References:

[3] - The present standard therapies, such as dietary protein restriction, arginine therapy, and nitrogen-scavenging therapy with either benzoate or phenylbutyrate, ... [4] - Nitric-oxide supplementation for treatment of long-term complications in argininosuccinic aciduria. Sandesh CS Nagamani. [5] - Long-term therapy should involve a low-protein diet and arginine supplementation. This diet helps produce equivalent quantities of ornithine for enhancement of ... [8] - Nitrates are not a standard treatment for ASA, but may be used in some cases to reduce ammonia levels in the blood. [9] - These drugs work by providing alternative pathways for nitrogen excretion. ... Argininosuccinic Aciduria Treatment. The treatment of ASA is a lifelong commitment, involving a combination of dietary management, medications, and, in some cases, surgical interventions.

Differential Diagnosis of Argininosuccinic Aciduria

Argininosuccinic aciduria, also known as argininosuccinate lyase deficiency (ASLD), is a rare inherited disorder that affects the urea cycle. The differential diagnosis of this condition involves identifying other possible causes of similar symptoms and laboratory findings.

Other Urea Cycle Disorders

The following disorders can present with similar symptoms to argininosuccinic aciduria:

• Carbamoyl-phosphate synthetase 1 deficiency: This disorder also affects the urea cycle and can cause hyperammonemia, a key feature of argininosuccinic aciduria.
• Ornithine transcarbamylase deficiency: Another urea cycle disorder that can present with similar symptoms to argininosuccinic aciduria, including hyperammonemia.
• Citrullinemia type I: A rare disorder caused by a deficiency of the enzyme argininosuccinate synthetase, which can also lead to hyperammonemia and other symptoms similar to argininosuccinic aciduria.
• Arginase deficiency: This disorder affects the final step of the urea cycle and can cause hyperammonemia and other symptoms similar to argininosuccinic aciduria.

Key Features for Differential Diagnosis

To differentiate argininosuccinic aciduria from these other disorders, clinicians should look for the following key features:

• Presence of argininosuccinate in plasma or urine: The presence of this compound is a hallmark of ASLD and can help distinguish it from other urea cycle disorders.
• Elevation of plasma citrulline together with elevated argininosuccinic acid: This biochemical profile is typical of ASLD and can be used to differentiate it from other disorders that affect the urea cycle.

References

• [1] The prevalence at birth of argininosuccinic aciduria (ASA) ranges between 1/70,000-218,000 worldwide. [12]
• [2] Presence of argininosuccinate in plasma or urine was mandatory in order to make a diagnosis of ASL deficiency/argininosuccinic aciduria. [12]
• [3] The biochemical diagnosis of ASLD is typically established with elevation of plasma citrulline together with elevated argininosuccinic acid in the plasma or urine. [13]

Note: The numbers in square brackets refer to the search results provided in the context, which were used to generate this answer.