Argininosuccinic Aciduria, Metabolic Disorder, Amino acid disorder Screening -Infant

Argininosuccinic Aciduria, Metabolic Disorder, Amino acid disorder Screening -Infant

Argininosuccinic Aciduria, Metabolic Disorder, Amino acid disorder Screening

Summary of Recommendation and Evidence

Population

Recommendation

Grade
(What's This?)

Screening of both genders

The genetic screening for Argininosuccinic Aciduria is recommended.

B

Argininosuccinic aciduria is a rare genetic disorder characterized by deficiency or lack of the enzyme argininosuccinate lyase (ASL). This enzyme is one of six enzymes that play a role in the breakdown and removal of nitrogen from the body, a process known as the urea cycle. The lack of this argininosuccinate lyase results in excessive accumulation of nitrogen, in the form of ammonia (hyperammonemia), in the blood. Excess ammonia travels to the central nervous system through the blood, resulting in the symptoms and physical findings associated with the disorder. 

OVERVIEW

A urea cycle disorder characterized by hyperammonemia and encephalopathy. The enzyme argininosuccinic acid lyase is deficient, blocking conversion of argininosuccinate to fumarate and arginine. This disease differs from other urea cycle defects because it causes chronic liver disease or isolated mental retardation (in very mild forms).

SCREENING

Finding

Elevated citrulline and argininosuccinic acid.

Tested By

Tandem mass spectrometry (MS/MS); sensitivity=NA; specificity=NA

PREVALENCE

Approximately 1 in 70,000 live births.

INHERITANCE

ASAL is inherited in an autosomal recessive manner. It affects both boys and girls equally.

PRENATAL TESTING

DNA testing possible by amniocentesis or chorionic villus sampling (CVS) if both disease causing mutations of an affected family member have been identified. Enzyme testing possible by amniocentesis or CVS.

Other Testing

Genetic testing is possible for at-risk family members if both disease causing mutations of an affected family member have been identified.

CLINICAL CHARACTERISTICS

With treatment before hyperammonemic crises, normal mental and physical development is possible. The results of newborn screening can return after the infant is already symptomatic. Without treatment, symptoms usually begin a few days after birth. Less severe variants may present in childhood. Acute symptoms may occur during prolonged fasting, periods of increased energy demands (fever, stress, lack of sleep), and after meals high in protein. 

Initial symptoms may include:

  • Poor appetite
  • Vomiting
  • Irritability
  • Seizures
  • Lethargy
  • Lab findings:
  1. Hyperammonemia
  2. Elevated transaminases
  3. Prolonged PT/PTT
  4. Elevated citrulline
  5. Elevated glutamine
  6. Elevated argininosuccinic acid
  7. Elevated urine orotic acid

Subsequent symptoms may include:

  • Poor growth/failure to thrive
  • Liver enlargement
  • Muscle weakness
  • Short, dry, brittle hair (trichorrhexis nodosa)
  • Cerebral edema
  • Seizures
  • Mental retardation
  • Death

EARLY SIGNS

There are two main forms of arginosuccinic aciduria (ASA), which differ in the age of onset. The first and most common form is seen in newborns. The first signs of ASA usually begin in the first few days after birth.

The second form is less common and is seen in children. Sometimes signs of ASA might not become apparent until late infancy or early childhood. In these cases, the signs are usually less severe.

Signs of ASA in babies include:

  • Poor appetite
  • Sleeping longer or more often 
  • Tiredness
  • Irritability
  • Vomiting
  • Trouble breathing
  • Seizures (also called epilepsy)
  • Involuntary or uncontrolled body movements
  • Delayed growth

Many of these signs may occur when your baby eats foods that his or her body cannot break down. They can be triggered by long periods of time without eating, illnesses, and infections.

CAUSES

When we eat food, enzymes help break it down. Some enzymes break down proteins into their building blocks, called amino acids. Other enzymes break down these amino acids. When we break down proteins, our bodies need even more enzymes to get rid of waste products. In arginosuccinic aciduria, the enzyme arginosuccinic acid lyase (ASAL) is not working correctly.

ASAL’s job is to help get rid of ammonia by breaking it down into urine. Ammonia is a waste product of protein breakdown.?

Babies with argininosuccinic aciduria (ASA) either do not make enough or make non-working ASAL. When ASAL does not work correctly, the body cannot remove ammonia through the urine. This causes a dangerous build-up of ammonia in the body.

ASA is an autosomal recessive genetic condition. This means that a child must inherit two copies of the non-working gene for ASA, one from each parent, in order to have the condition. The parents of a child with an autosomal recessive condition each carry one copy of the non-working gene, but they typically do not show signs and symptoms of the condition. While having a child with ASA is rare, when both parents are carriers, they can have more than one child with the condition.

TREATMENT

Dietary Treatment

Your baby may need to follow a low-protein diet to avoid certain foods that he or she cannot break down. A dietician or nutritionist can help you plan the appropriate diet for your child’s healthy growth.

Your baby’s doctor might also recommend special formulas and foods for children with arginosuccinic aciduria (ASA). These formulas will likely need to continue through adulthood.

Supplements and Medications

Many babies with ASA take arginine supplements.  Arginine is a natural substance, and it can help lower the high ammonia levels that result from ASA. Everyone has some ammonia in his or her blood, but high levels can be toxic. Your baby’s doctor can write you a prescription for these supplements.

EXPECTED OUTCOMES

When arginosuccinic aciduria (ASA) is treated early, children can have healthy growth and development. This is why screening for ASA is so important. Newborn screening can allow for treatment before ammonia levels become dangerously high in your baby’s bloodstream.

Some children still have high ammonia levels in their blood even with treatment. These children may need to seek treatment in a hospital to remove the ammonia from their blood.

It is very important to treat ASA. Babies who do not receive treatment are at risk for intellectual disabilities, developmental delays, liver damage, brain damage, coma, or death.