CITRULLINEMIA TYPE I (CTLN1)
ASS Sequencing
DNA ANALYSIS

Citrullinemia type I (CTLN1) is an autosomal recessive disorder resulting from deficiency of the enzyme argininosuccinate synthase (ASS), the third step in the urea cycle, in which citrulline is condensed with aspartate to form arginosuccinic acid As with other urea cycle disorders, the age of presentation can vary, however the most common presentation is in the neonatal period. Affected infants become hyperammonemic and may experience vomiting, refusal to eat, progressive lethargy, and coma. Other than the acute neonatal form (the "classic" form), there is a milder late-onset form, and a rarely reported adult form . The ASS gene is localized to chromosome 9q34.1 and consists of 16 exons of which 14 are coding exons. Sequence analysis of the coding region of the ASS gene is available on a clinical basis at the Medical Genetics Laboratories at Baylor College of Medicine.

Reasons for Referral:

Confirmation of biochemical diagnosis in affected individuals.
Identification of mutations in proband to facilitate carrier testing.
Prenatal diagnosis (Both known mutations only).

Testing Methodology:

Full Sequencing: A PCR-based assay is used to amplify all 16 exons of the ASS gene. Direct sequencing of amplification products is performed in both the forward and reverse directions using automated fluorescence dideoxy sequencing methods.

Sensitivity:

Clinical: Approximately 90%
Analytical: > 98%

Specimen Requirements:

Blood for DNA: EDTA (purple-top) tubes: Adult/Child: Minimum 6-14 cc
Requisition form must accompany the specimen. Prior to any genetic testing, we recommend genetic counseling and we request that the subject sign our consent statement and submit it with the sample. To receive forms, additional information or specimen collection kits, please contact the laboratory. Please call laboratory for specific requirements for prenatal testing.

Turnaround Time:

Index: 4 weeks
Known Familial Mutation: 3 weeks

CPT Codes and Prices:

Index: 83904X30, 83912, 83909x30, 83898x15, 83894, 83891
Known Familial Mutation: 83904x2, 83912, 83909x2, 83898, 83891, 83894

References:

1. Beaudet AL, O'Brien WE, Bock HG, Freytag SO, Su TS. (1986) The human argininosuccinate synthetase locus and citrullinemia. Adv. Hum. Genet. 15: 161-196, 291-292.
2. Saheki T, Kobayashi K, Lijima M, Nishi I, Yasuda T, Yamaguchi N, Gao HZ, Jalil MA, Begum L, Li MX. (2002) Pathogenesis and pathophysiology of citrin (a mitochondrial aspartate glutamate carrier) deficiency. Metab. Brain Dis. 17: 335-346. Review.

Shipping Information

Forms:

>> Gene Sequencing Requisition
>> Prenatal Requisition

Test Codes:

Index: 6180
Known Familial Mutation: 6185
Prenatal (Known Familial Mutation Only): 6190