UGT1A1-related disorders in Bahrain: A genetic and clinical overview of Crigler-Najjar and Gilbert syndromes
Abstract
BACKGROUND: UGT1A1-related disorders, including Crigler-Najjar syndrome (CNS) type I, type II, and Gilbert syndrome (GS), disrupt bilirubin metabolism, resulting in unconjugated hyperbilirubinemia.
AIM: To evaluate the prevalence of UGT1A1-related disorders and compare clinical features, genetic variations, management, and outcomes across the three phenotypes.
METHODS: We conducted a retrospective cohort study at the Department of Pediatrics, Salmaniya Medical Complex, Government Hospitals, Bahrain, between 2004 and 2024. This hospital is the only national referral center for genetic services in Bahrain. Of 55 suspected cases, 35 patients (63.6%) were genetically confirmed to have UGT1A1-related disorders. The three phenotypes were compared regarding clinical characteristics, biochemical parameters, genetic variations, treatment, and outcomes. Fisher’s exact test, Student’s t-test, the Mann–Whitney U test, and paired t-test were used for comparison.
RESULTS: The estimated national disease prevalence was 2.2 per 100000 individuals. GS was the most common phenotype (n = 27, 77.1%), followed by CNS-II (n = 7, 20.0%) and CNS-I (n = 1, 2.9%). Parental consanguinity was reported in 40.0% of cases. CNS-I was diagnosed earlier, at 6 months of age, than CNS-II [11.3 (0.3-16.8) years] and GS [13.4 (11.9-16.9) years]. Glucose-6-phosphate dehydrogenase deficiency was the most common coexisting condition (48.6%). Total bilirubin level at presentation was higher in CNS-I (409 μmol/L) than CNS-II (105.3 ± 46.2 μmol/L) and GS (88.2 ± 53.8 μmol/L). Homozygous (TA)7/7 polymorphism in the UGT1A1 promoter was the most common variant (91.4%). CNS-I required continuous phototherapy then liver transplantation, achieving sustained bilirubin normalization over 16.7 years of follow-up. Among patients with CNS-II, 85.7% were treated with phenobarbital, whereas 48.1% of patients with GS received phenobarbital before diagnosis, with poor adherence in 78.9% of cases. In CNS-II, there was no significant difference between indirect bilirubin level at presentation and at follow-up (92.3 ± 47.6 μmol/L vs 90.9 ± 58.0 μmol/L, P = 0.969).
CONCLUSION: Although rare, UGT1A1-related disorders represent important causes of unconjugated hyperbilirubinemia in Bahrain, with GS being the most prevalent phenotype. Genetic testing is essential for accurate diagnosis and appropriate management, particularly in patients with coexisting hematological conditions.
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BibTeX
@article{isa2026ugt1a1related,
title = {{UGT1A1-related disorders in Bahrain: A genetic and clinical overview of Crigler-Najjar and Gilbert syndromes}},
author = {Hasan M Isa and Fatema A Abdulaal and Maryam Y Busehail and Maryam H Kamal and Hawra A Alaswad and Fatima Y Alshaikh and Aysha A Aljassmi and Anfal J Hijris},
journal = {World Journal of Clinical Pediatrics},
year = {2026},
month = nov,
doi = {10.5409/wjcp.121263},
url = {https://doi.org/10.5409/wjcp.121263},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - UGT1A1-related disorders in Bahrain: A genetic and clinical overview of Crigler-Najjar and Gilbert syndromes
AU - Hasan M Isa
AU - Fatema A Abdulaal
AU - Maryam Y Busehail
AU - Maryam H Kamal
AU - Hawra A Alaswad
AU - Fatima Y Alshaikh
AU - Aysha A Aljassmi
AU - Anfal J Hijris
PY - 2026
DA - 2026/11/03
JO - World Journal of Clinical Pediatrics
DO - 10.5409/wjcp.121263
UR - https://doi.org/10.5409/wjcp.121263
AB - BACKGROUND: UGT1A1-related disorders, including Crigler-Najjar syndrome (CNS) type I, type II, and Gilbert syndrome (GS), disrupt bilirubin metabolism, resulting in unconjugated hyperbilirubinemia. AIM: To evaluate the prevalence of UGT1A1-related disorders and compare clinical features, genetic variations, management, and outcomes across the three phenotypes. METHODS: We conducted a retrospective cohort study at the Department of Pediatrics, Salmaniya Medical Complex, Government Hospitals, Bahrain, between 2004 and 2024. This hospital is the only national referral center for genetic services in Bahrain. Of 55 suspected cases, 35 patients (63.6%) were genetically confirmed to have UGT1A1-related disorders. The three phenotypes were compared regarding clinical characteristics, biochemical parameters, genetic variations, treatment, and outcomes. Fisher’s exact test, Student’s t-test, the Mann–Whitney U test, and paired t-test were used for comparison. RESULTS: The estimated national disease prevalence was 2.2 per 100000 individuals. GS was the most common phenotype (n = 27, 77.1%), followed by CNS-II (n = 7, 20.0%) and CNS-I (n = 1, 2.9%). Parental consanguinity was reported in 40.0% of cases. CNS-I was diagnosed earlier, at 6 months of age, than CNS-II [11.3 (0.3-16.8) years] and GS [13.4 (11.9-16.9) years]. Glucose-6-phosphate dehydrogenase deficiency was the most common coexisting condition (48.6%). Total bilirubin level at presentation was higher in CNS-I (409 μmol/L) than CNS-II (105.3 ± 46.2 μmol/L) and GS (88.2 ± 53.8 μmol/L). Homozygous (TA)7/7 polymorphism in the UGT1A1 promoter was the most common variant (91.4%). CNS-I required continuous phototherapy then liver transplantation, achieving sustained bilirubin normalization over 16.7 years of follow-up. Among patients with CNS-II, 85.7% were treated with phenobarbital, whereas 48.1% of patients with GS received phenobarbital before diagnosis, with poor adherence in 78.9% of cases. In CNS-II, there was no significant difference between indirect bilirubin level at presentation and at follow-up (92.3 ± 47.6 μmol/L vs 90.9 ± 58.0 μmol/L, P = 0.969). CONCLUSION: Although rare, UGT1A1-related disorders represent important causes of unconjugated hyperbilirubinemia in Bahrain, with GS being the most prevalent phenotype. Genetic testing is essential for accurate diagnosis and appropriate management, particularly in patients with coexisting hematological conditions.
SN - 2219-2808
ER -