Test Code: 8709

Citrullinemia: ASS1 Gene Deletion/Duplication
Test Code: 8709
Turnaround time: 3 weeks


Citrullinemia type I (CTLN1) is an autosomal recessive disorder resulting from a deficiency of the enzyme argininosuccinate synthase (ASS), the third step in the urea cycle, in which citrulline is condensed with aspartate to form argininosuccinic acid. Laboratory findings include hyperammonemia (ammonia concentration 1000-3000 mol/L in plasma), while analysis of plasma quantitative amino acids shows an absence of argininosuccinic acid and a concentration of citrulline usually greater than 1000 mol/L (normal: <50 mol/L). Argininosuccinate synthase enzyme activity, measured in fibroblasts, liver, and in all tissues in which ASS is expressed, is decreased.

The disease presents as a clinical spectrum that includes an acute neonatal form (the “classic” form), a milder late-onset form, and a form in which women have onset of severe symptoms during pregnancy or postpartum. Individuals remaining asymptomatic up to at least age ten have also been reported. Distinction between the clinical forms is based on clinical findings and is not clear-cut. Classic neonatal-onset citrullinemia type I is suspected in infants who have been on a full protein diet and who present in the first week of life with hyperammonemia, lethargy, refusal to feed, and vomiting. Hyperammonemia may lead to increased intracranial pressure, which can cause increased neuromuscular tone, spasticity, ankle clonus, seizures, loss of consciousness, and death. Children with the severe form who are treated promptly may survive for an indeterminate period of time, but usually with significant neurologic deficits. Milder, adult-onset citrullinemia type I is suspected in individuals with recurrent lethargy, somnolence, mental retardation, and chronic or recurrent hyperammonemia. CTLN1 occurs in 1:57,000 births.

Citrullinemia type I is caused by mutations in the ASS1 gene (9q34.1). Sequencing of the ASS1 gene is recommended after a biochemical diagnosis of CTLN1, and provides a complementary method to confirm the presence of mutations in a proband, identify carriers among the proband’s relatives, and provide prenatal diagnosis in families with known mutations.

• OMIM #215700: Citullinemia, Classic


This test is indicated for:

  • Confirmation of a clinical/biochemical diagnosis of citrullinemia type I
  • Carrier testing in adults with a family history of citrullinemia type I


DNA isolated from peripheral blood is hybridized to a CGH array to detect deletions and duplications. The targeted CGH array has overlapping probes which cover the entire genomic region.

Please note that a “backbone” of probes across the entire genome are included on the array for analytical and quality control purposes. Rarely, off- target copy number variants causative of disease may be identified that may or may not be related to the patient’s phenotype. Only known pathogenic off-target copy number variants will be reported. Off-target copy number variants of unknown clinical significance will not be reported.


Detection is limited to duplications and deletions. Array CGH will not detect point mutations or intronic mutations. Results of molecular analysis must interpreted in the context of the patient’s clinical and/or biochemical phenotype.


Submit only 1 of the following specimen types
* Preferred specimen type: Whole Blood

Type: Whole Blood
Specimen Requirements:
In EDTA (purple top) or ACD (yellow top) tube: Infants (2 years): 3-5 ml
Older Children & Adults: 5-10 ml

Specimen Collection and Shipping: Refrigerate until time of shipment. Ship sample within 5 days of collection at room temperature with overnight delivery.

Type: Saliva
Specimen Requirements:
OrageneTM Saliva Collection kit (available through CEN4GEN) used according to manufacturer instructions.

Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.

Submit copies of diagnostic biochemical test results with the sample. Sequence analysis is required before deletion/duplication analysis by targeted CGH array. If sequencing is performed by another third party provider, please submit a copy of the sequencing report with the test requisition.

• Custom diagnostic mutation analysis (test code: 6875) is available to family members if mutations are identified by sequencing.