Argininosuccinic Aciduria (ASA)
(Argininosuccinic lyase deficiency)

Introduction
ASA is the second most common urea cycle disorder with an incidence of about
1:70,000. As with other urea cycle disorders the major problem is an impaired ability to
excrete nitrogen as urea causing a neurotoxic accumulation of ammonia. This problem is
most marked during the catabolic newborn period, infections or following a protein
overload. Inheritance is autosomal recessive. Major sequelae

Clinical Features
Neonatal
Lethargy
Poor feeding
Hypotonia
Apnea/tachypnea
Hepatomegaly
Seizures
Death
Infancy/childhood
Episodic vomiting
Lethargy
Hepatomegaly
Developmental delay
Ataxia
Dry, brittle hair ("trichorrhexis nodosa")
Consequences

Diagnosis
Newborn screen
Tandem mass spectrometry of newborn blood filter paper specimen
     (demonstrating elevated citrulline)
Confirmation
Red Blood Cell enzyme activity

Treatment
Low protein diet
L-arginine supplementation
Situations that risk metabolic decompensation
Catabolic processes such as infection, after an immunization, during prolonged fasting
or after dietary overload. This can lead to hyperammonemia and clinical decompensation necessitating emergency treatment.

Monitoring
Clinical observation is the most important tool. Observe for Increased lethargy, recurrent
vomiting, anorexia, tachypnea or apnea. Metabolic decompensation may occur in the
absence of hyperammonemia thus treatment should be led by the clinical picture and
not be based solely on ammonia levels.

STAT emergency treatment
Stop protein intake. L-Arginine as well as fluids must be administered IV. Start IV 10%
dextrose (and later intralipid) to maintain caloric intake approaching 100kcal/kg/day.
Parents usually have an emergency protocol with them, which contains basic information
about the disorder, necessary clinical tests and guidelines for treatment.
n.b. To ensure accurate ammonia measurements it is important to obtain a free flowing
blood sample, place it on ice and send to the lab STAT.

Infection/Immunization
Any infection can potentially lead to metabolic decompensation. Therefore its prevention
and/or early intervention is of particular importance. For this and other reasons
immunizations must be kept on track. This includes a yearly vaccine for influenza for all children with ASA. There is no contraindication to immunization because of ASA, but
patients and physicians should be alerted to the need for immediate evaluation if high
fever, lethargy or vomiting occurs in the first 24h. After an immunization without any
other clinical symptoms, administration of acetaminophen or ibuprofen is warranted.

Surgical/surgical procedures
Anesthesia and surgery place the patient with ASA at a particular risk for metabolic
decompensation, mainly caused by preoperative fasting. Consequently, fasting must be
avoided to the fullest extent possible. If surgery is required, it is imperative that before
starting fasting, the patient receives IV fluids with high caloric support. This needs to be
continued through the operation and postoperatively until normal eating is restored.
Moreover, general anesthesia with enflurane has been associated with metabolic
decompensation and sudden death in ASA patients. Any surgery should include
hospitalization pre- and postoperatively at a hospital with a pediatric metabolic
service.

Growth and development
As with any child on a special dietary regime, regular monitoring of growth parameters
becomes particularly important. The local early intervention program should assess any
neurological/behavioral problems early. It is hoped that pre-symptomatic identification of
ASA by expanded newborn screening and early treatment will prevent, or at least
improve, long-term neurological problems that have been a major problem, particularly in
the neonatal onset cases. Early treatment of late onset ASA can result in normality.

Figure