Argininosuccinic aciduria (OMIM 207900) is an autosomal recessive disorder of the urea cycle, caused by deficiency of argininosuccinate lyase (ASL), which catalyzes the degradation of argininosuccinate to fumarate and arginine. Two main types of ASL deficiency have been described and vary according to age of onset and clinical manifestations. The neonatal type is characterized by poor feeding, vomiting, lethargy and seizures, with progression to coma and death if untreated. In contrast, patients with onset in late infancy present with less severe symptoms, which include vomiting, failure to thrive, irritability, behavioral problems, mental retardation and developmental delay. Biochemical diagnosis in clinically suspected patients is made by the measurement of ammonia and specifically, argininosuccinic acid and its anhydrides. The human ASL gene is approximately 17 kb in length, is comprised of 16 coding exons and is located on chromosome 7q11.2. Sequence analysis of the coding region of the ASL gene is available on a clinical basis at the Medical Genetics Laboratories at Baylor College of Medicine.

Reasons for Referral:

• Confirmation of a clinical diagnosis of Argininosuccinic aciduria.
• Carrier testing for individuals with a positive family history for an ASL point mutation (molecular analysis of the affected relative is recommended).
• Prenatal diagnosis for families at 1 in four risk.

Testing Methodology: PCR amplification of the exons contained in the ASL gene coding regions will be performed on patient genomic DNA. Direct sequencing of amplification products is performed in both the forward and reverse directions using automated fluorescence dideoxy sequencing methods.

Specimen Requirements:
Blood: EDTA (purple-top) tubes: Adults: 14 cc; Child: 6 cc; Infant: 2-3 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: 4 weeks

CPT Codes and Prices:
Index: 83891, 83898x13, 83894, 83904x26, 83909x26, 83912
Known Familial Mutation: 83891, 83898, 83894, 83904x2, 83909x2, 83912

References:
1. Allan JD, Cusworth DC, Dent CE; Wilson VK. A disease, probably hereditary, characterized by severe mental deficiency and a constant gross abnormality of amino acid metabolism. Lancet I: 182-187, 1958.

2. Linnebank M, Tschiedel E, Haberle J, Linnebank A, Willenbring H, Kleijer WJ, Koch HG. Argininosuccinate lyase (ASL) deficiency: mutation analysis in 27 patients and a completed structure of the human ASL gene. Hum. Genet. 111: 350-359, 2002.

3. Kleijer WJ, Garritsen VH, Linnebank M, Mooyer P, Huijmans JGM, Mustonen A, Simola KOJ, Arslan-Kirchner M, Battini R, Briones P, Cardo E, Mandel H, Tschiedel E, Wanders RJA, Koch HG. Clinical, enzymatic, and molecular genetic characterization of a biochemical variant type of argininosuccinic aciduria: prenatal and postnatal diagnosis in 5 unrelated families. J. Inherit. Metab. Dis. 25: 399-410, 2002. 

Shipping Information

Forms:
 >> Gene Sequencing Requisition
 >> Prenatal Requisition

Test Codes:
Index: 6360
Known Familial Mutation: 6361
Prenatal: 6362

Last Modified: 3-3-08