Diagnostic Criteria

Suggested guidelines for the diagnosis of argininosuccinate lyase deficiency (ASLD) have been published .

Suggestive Findings

ASLD should be suspected in:

• An infant with (NBS) result;

• An infant with ;

• An individual at any age with (including late-onset ASLD).

Infant with Out-of-Range NBS Result

NBS for ASLD is primarily based on use of dried blood spots collected between 24 and 72 hours after birth to quantify citrulline concentrations by tandem mass spectrometry (MS/MS). In the United States most NBS laboratories determine their own levels for results that are considered out of range. For information on NBS by state in the US, see www.newbornscreening.hrsa.gov/your-state. Immediately on receipt of out-of-range NBS results (i.e.

Source: GeneReviews — "Argininosuccinate Lyase Deficiency"

Differential Diagnosis

Elevated citrulline. Elevation of citrulline can be seen in other disorders such as citrullinemia type 1, citrin deficiency, pyruvate carboxylase deficiency, and dihydrolipoamide dehydrogenase deficiency. Neonatal-onset arginosuccinate lyase deficiency (ASLD). The clinical presentation of neonatal-onset ASLD is indistinguishable from that of other urea cycle disorders (UCDs) (see Urea Cycle Disorders Overview). Late-onset ASLD. A late-onset phenotype may be seen in other UCDs (e.g., ornithine transcarbamylase deficiency and citrullinemia type I); however, elevated argininosuccinate on plasma and/or urine amino acids is pathognomonic of ASLD and differentiates ASLD from these UCDs.

Source: GeneReviews — "Argininosuccinate Lyase Deficiency"

Management Guidelines

When arginosuccinate lyase deficiency (ASLD) is suspected during the diagnostic evaluation due to , metabolic treatment should be initiated immediately. Development and evaluation of treatment plans, training and education of affected individuals and their families, and avoidance of adverse effects of dietary treatment (i.e., malnutrition, growth failure) require a multidisciplinary approach including multiple subspecialists, with oversight and expertise from a specialized metabolic center.

Evaluation of a Newborn with an Out-of-Range NBS Result

Table 2.

Arginosuccinate Lyase Deficiency: Recommended Evaluations Following an Out-of-Range Newborn Screening Result

System/Concern | Evaluation | Comment

Biochemical

| Consultation w/metabolic physician/ biochemical geneticist specialist metabolic dietitian1 | • Transfer to specialist center w/experience in management of inherited metabolic diseases (strongly recommended).

• Consider short hospitalization at a center of expertise for inherited metabolic conditions to provide caregivers w/detailed education (natural history, maintenance emergency treatment, prognosis, risks for acute encephalopathic crises).

Laboratory eva | • Plasma ammonia

• Plasma (or urine) amino acids

• Urine organic acids

Surveillance Guidelines

In addition to regular evaluations by a metabolic specialist and metabolic dietician, the evaluations summarized in are recommended to monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations.

Table 9.

Argininosuccinate Lyase Deficiency: Recommended Surveillance

Manifestation/Concern | Evaluation | Frequency/Comment

Metabolic

| Assessment w/metabolic dietician clinical biochemical geneticist incl:

• Height, weight, body mass index

• Laboratory indices of nutritional status (e.g., prealbumin, BCAAs [leucine, isoleucine, valine], plasma amino acids, plasma ammonia to identify deficiency of essential amino acids assess for impending hyperammonemia1

• Phenylbutyrate metabolite levels may be used for monitoring persons on phenylbutyrate medications.

| Lab clinical monitoring frequency depend on metabolic status of affected person. In general:

• Neonates: every 2 wks

• Infants (age 2 mos-1 yr): every 1-3 mos

• Children (age ≥2 yrs): every 3-4 mos

Development/ Neurobehavioral issues

| • Assess developmental progress educational needs.

• Behavioral assessment incl ADHD assessment

| Annually or as needed

Seizures/ Abnormal motor function coordination

| • Assess for new manifestations such as seizures, abnormal motor function, problems w/coordination.

• PT /or OT assessment as needed

| At each visit

Liver disease

| ALT, AST, liver function testing (albumin, INR) | Every 6-12 mos or as needed

Liver ultrasound | Consider every 1-2 yrs.2

Source: GeneReviews — "Argininosuccinate Lyase Deficiency"