Guidance for primary care clinicians receiving a positive newborn screen result

Other Names

ICD-10 Coding

Disorder Category

Abnormal Finding

Tested By

Argininosuccinic aciduria is a urea cycle disorder resulting from deficiency of the enzyme argininosuccinate lyase, disrupting the conversion of argininosuccinate to fumarate and arginine. As with most other urea cycle disorders, it is characterized by hyperammonemia and encephalopathy. However, the common finding of chronic liver disease, trichorrhexis nodosa, and systemic hypertension, often despite optimal metabolic management, is unique to argininosuccinic aciduria. Though commonly considered a disease of severe neonatal onset, late-onset cases in childhood to late adulthood have been reported, typically with a hyperammonemic crisis triggered by an acute infection.

Clinical Characteristics

Incidence

Inheritance

Next Steps After a Positive Screen

• Contact the family, inform them of the newborn screening result, and evaluate the infant for clinical symptoms (poor feeding, vomiting, lethargy, tachypnea).
• Immediately consult with Medical Genetics (see NV providers [5]).
• Measure the blood ammonia and initiate emergency treatment or referral if there is evidence of hyperammonemia or clinical symptoms, such as vomiting, refusal of feeds, lethargy, or seizures. See the ACT Sheet for Elevated Citrulline (ACMG) for other immediate steps to take upon notification of a positive screen.

Confirming the Diagnosis

• To confirm the diagnosis of argininosuccinic aciduria, work with Newborn Screening Services (see NV providers [2]).
• Quantitative plasma ammonia and amino acid analysis, urine orotic acid
• Genetic Testing and Counseling (see NV providers [11]) is possible for at-risk family members if both disease-causing mutations of an affected family member have been identified.

If the Diagnosis is Confirmed

• For evaluation and ongoing collaborative management, consult Biochemical Genetics (Metabolics) (see NV providers [2]).
• Educate the family regarding signs, symptoms, and the need for urgent care when the infant becomes ill. See Argininosuccinic Acid Lyase Deficiency - Information for Parents (newbornscreening.info).
• Assist in implementing and supporting a low-protein diet and arginine and essential amino acid supplements.
• Ammonia scavenging medications (e.g., sodium benzoate or sodium phenylbutyrate) are usually indicated and prescribed by pediatric genetics.
• Regular blood tests to monitor amino acid and ammonia levels may be indicated.
• Immediate hospital admission may be required during episodes of hyperammonemia or illness.
• For those identified after irreversible consequences, assist in management, particularly with developmental and educational interventions. Refer to Early Intervention for Children with Disabilities/Delays (see NV providers [31]) as needed.