BACKGROUND AND OBJECTIVES:
Gilbert syndrome is an underdiagnosed clinical entity because >30% of patients are asymptomatic. The clinical and genetic patterns have not been fully elucidated. Several genetic association studies have linked a number of single nucleotide polymorphisms (SNPs) with unconjugated hyperbilirubinemia. We conducted the current study to investigate the different clinical presentations and to validate the association of SNPs with the development of hyperbilirubinemia in patients with Gilbert syndrome in the Kingdom of Saudi Arabia.
Screening of patients attending the outpatient clinics identified 65 patients with Gilbert syndrome, who were enrolled in the study. Complete laboratory workup, abdominal ultrasound, and abdominal computed tomography were performed. Genotyping of 5 SNPs in 2 candidate genes was conducted in all patients with hyperbilirubinemia, in addition to 100 controls, by polymerase chain reaction restriction fragment length polymorphism, gene scan analysis, and direct DNA sequencing.
The study cohort included 27 male and 38 female patients (age range 12–32 years, mean 18 ± 12.8 years). The cohort included 40 Saudi, 12 Indian, 9 Jordanian, and 4 Filipino patients. Jaundice was the only manifestation in 45% of cases. Nonspecific symptoms such as abdominal cramps, fatigue, and malaise were reported in 40% of cases, and 15% of patients were asymptomatic. Genetic polymorphisms of the UGT1A1 promoter, specifically the −3279 T→G phenobarbital responsive enhancer module (rs4124874) and (TA)7 dinucleotide repeat (rs8175347) and the coding region variants (rs2306283 and rs4149056) of the OATP2 gene, were significantly higher among the cases than among the controls.
Gilbert syndrome should be suspected in patients with unexplained hyperbilirubinemia or nonspecific symptoms. The UGT1A1 polymorphisms and number of variants are associated with altered bilirubin metabolism and could be genetic risk factors for neonatal hyperbilirubinemia.
- Copyright © 2015 by the American Academy of Pediatrics