Heparinized specimens, severely hemolyzed specimens, frozen, clotted or possibly commingled specimens, blood in non-sterile or leaky containers, mislabeled or inappropriately labeled specimens.
Storage/Transport Temperature
For CHOP Phlebotomy: Samples can be collected throughout the week. Samples collected on weekends or holidays are held in Central Labs and sent to the Genomic Diagnostic Lab the following business day.
For External Clients: Refrigerate sample until shipment. Send the sample at room temperature with overnight delivery for receipt Monday through Friday, optimally within 24 hours of collection.
Please contact the lab (267-426-1447) with questions regarding non-blood specimens.
Volume Required
5 ml
Minimum Required
3 ml
Phlebotomy Draw
Yes
Clinical Features
Gilbert's syndrome, a common phenotype found in approximately 3-10% of the general population, is characterized by mild, chronic, unconjugated hyperbilirubinemia in the absence of liver disease or overt hemolysis. The diagnosis of this disorder is made on the observation of elevated unconjugated bilirubin levels and normal liver function. The importance of the diagnosis of this benign syndrome is to rule out more serious liver disease as the underlying cause of the hyperbilirubinemia. Individuals with Gilbert's syndrome have a reduced level of hepatic bilirubin UDP-glucuronosyltransferase 1A1 (UGT1A1), the enzyme necessary for the conjugation of bilirubin.
Performing Lab
Division of Genomic Diagnostics
Performed
Mon - Fri 9:00am to 4:00pm
Reported
10 days
Detection Rate
The analytical sensitivity for sequencing is close to 100%. Approximately 98% of patients with Gilbert's syndrome will be homozygous or compound heterozygotes for two abnormal TA repeat alleles.
Utility
Gilbert's syndrome is considered benign in adults, although an incidental finding of hyperbilirubinemia may raise the possibility of liver disease and so trigger unnecessary investigational testing. Co-inheritance of Gilbert's syndrome and a known hemolytic disorder such as beta thalassemia or sickle cell anemia may go undetected due to already high levels of unconjugated bilirubin in these patients. However, these patients are at increased risk for developing gallstones at an early age. Confirmation of Gilbert's syndrome in these patients may lead to early intervention and treatment. Gilbert's syndrome is also associated with a higher chance of developing severe diarrhea and leucopenia during irinotecan therapy. Irinotecan is a potent chemotherapeutic drug commonly used for many types of cancer, in particular, gastrointestinal and pulmonary malignancies. Its active metabolite, SN-38, is glucuronidated by UGT1A1. The presence of the 7/7 genotype in UGT1A1 can lead to a 1.8-3.9 lower glucuronidation of SN-38 compared with patients with the wild type (6/6) resulting in dose limiting toxicity of irinotecan. Determination of UGT1A1 genotypes will aid in identifying those patients who have an increased risk of developing toxicity phenotypes with irinotecan treatment.
Synonyms
Hyperbilirubinemia I, UGT1A1, Gilbert Syndrome
UGT1A
LIS Mnemonic
UGT1A
Available STAT
No
Test Notes
We offer DNA fragment analysis of the promoter region of the UGT1A1 gene to detect all allele types. PCR amplification followed by fragment analysis is performed on the promoter region. The patient's fragment size is then compared to reference samples. Sequence variants are classified as A(TA)6TAA, A(TA)7TAA, A(TA)5TAA, and A(TA)8TAA.
Molecular Testing Notes
The UGT1A1 gene is located on chromosome 2q37. A polymorphism in the promoter region of the UGT1A1 gene has been identified in the majority of Caucasian individuals with Gilbert's syndrome (80-100%). Most individuals are homozygous for two extra bases (TA) in the promoter region of the gene and have an A(TA)7TAA sequence rather than an A(TA)6TAA sequence. This change is associated with reduced expression of the UGT1A1 gene. Other normal alleles with 5 TA repeats or abnormal alleles with 8 TA repeats have also been identified, although less commonly.
CPT Codes
81350
Billing (EAP) Codes
808016-UGT1A1 (Gilbert Syndrome)
Collection
Collect
Collect whole blood in a purple top (EDTA) tube.
Unacceptable Conditions
Heparinized specimens, severely hemolyzed specimens, frozen, clotted or possibly commingled specimens, blood in non-sterile or leaky containers, mislabeled or inappropriately labeled specimens.
Storage/Transport Temperature
For CHOP Phlebotomy: Samples can be collected throughout the week. Samples collected on weekends or holidays are held in Central Labs and sent to the Genomic Diagnostic Lab the following business day.
For External Clients: Refrigerate sample until shipment. Send the sample at room temperature with overnight delivery for receipt Monday through Friday, optimally within 24 hours of collection.
Please contact the lab (267-426-1447) with questions regarding non-blood specimens.
Volume Required
5 ml
Minimum Required
3 ml
Phlebotomy Draw
Yes
Ordering
Clinical Features
Gilbert's syndrome, a common phenotype found in approximately 3-10% of the general population, is characterized by mild, chronic, unconjugated hyperbilirubinemia in the absence of liver disease or overt hemolysis. The diagnosis of this disorder is made on the observation of elevated unconjugated bilirubin levels and normal liver function. The importance of the diagnosis of this benign syndrome is to rule out more serious liver disease as the underlying cause of the hyperbilirubinemia. Individuals with Gilbert's syndrome have a reduced level of hepatic bilirubin UDP-glucuronosyltransferase 1A1 (UGT1A1), the enzyme necessary for the conjugation of bilirubin.
Performing Lab
Division of Genomic Diagnostics
Performed
Mon - Fri 9:00am to 4:00pm
Reported
10 days
Detection Rate
The analytical sensitivity for sequencing is close to 100%. Approximately 98% of patients with Gilbert's syndrome will be homozygous or compound heterozygotes for two abnormal TA repeat alleles.
Utility
Gilbert's syndrome is considered benign in adults, although an incidental finding of hyperbilirubinemia may raise the possibility of liver disease and so trigger unnecessary investigational testing. Co-inheritance of Gilbert's syndrome and a known hemolytic disorder such as beta thalassemia or sickle cell anemia may go undetected due to already high levels of unconjugated bilirubin in these patients. However, these patients are at increased risk for developing gallstones at an early age. Confirmation of Gilbert's syndrome in these patients may lead to early intervention and treatment. Gilbert's syndrome is also associated with a higher chance of developing severe diarrhea and leucopenia during irinotecan therapy. Irinotecan is a potent chemotherapeutic drug commonly used for many types of cancer, in particular, gastrointestinal and pulmonary malignancies. Its active metabolite, SN-38, is glucuronidated by UGT1A1. The presence of the 7/7 genotype in UGT1A1 can lead to a 1.8-3.9 lower glucuronidation of SN-38 compared with patients with the wild type (6/6) resulting in dose limiting toxicity of irinotecan. Determination of UGT1A1 genotypes will aid in identifying those patients who have an increased risk of developing toxicity phenotypes with irinotecan treatment.
Synonyms
Hyperbilirubinemia I, UGT1A1, Gilbert Syndrome
UGT1A
LIS Mnemonic
UGT1A
Available STAT
No
Test Notes
We offer DNA fragment analysis of the promoter region of the UGT1A1 gene to detect all allele types. PCR amplification followed by fragment analysis is performed on the promoter region. The patient's fragment size is then compared to reference samples. Sequence variants are classified as A(TA)6TAA, A(TA)7TAA, A(TA)5TAA, and A(TA)8TAA.
Molecular Testing Notes
The UGT1A1 gene is located on chromosome 2q37. A polymorphism in the promoter region of the UGT1A1 gene has been identified in the majority of Caucasian individuals with Gilbert's syndrome (80-100%). Most individuals are homozygous for two extra bases (TA) in the promoter region of the gene and have an A(TA)7TAA sequence rather than an A(TA)6TAA sequence. This change is associated with reduced expression of the UGT1A1 gene. Other normal alleles with 5 TA repeats or abnormal alleles with 8 TA repeats have also been identified, although less commonly.
