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Should patients with symptomatic cholelithiasis before 30 years of age be tested for ABCB4 gene mutations?
Catarina Gouveia1, Margarida Flor de Lima2, Flávio Pereira3
1Gastroenterology Department, Hospital Beatriz Ângelo, Loures.
Insights
Low phospholipid-associated cholelithiasis syndrome (LPAC) is often missed in young adults. Genetic testing for ABCB4 mutations is most beneficial for patients meeting strict LPAC criteria.
Area of Science:
- Hepatology
- Genetics
- Gastroenterology
Background:
- Low phospholipid-associated cholelithiasis syndrome (LPAC) is linked to ABCB4 gene mutations, causing gallstones in young adults.
- Current diagnostic criteria are complex, leading to underdiagnosis of LPAC.
- The clinical utility of genetic testing for LPAC remains unclear.
Purpose of the Study:
- To determine the prevalence of ABCB4 gene mutations in patients under 30 with symptomatic cholelithiasis.
- To evaluate the diagnostic yield of genetic testing in this patient group.
Main Methods:
- A multicentric prospective cohort study was conducted in Portugal from 2017-2019.
- 32 patients with symptomatic cholelithiasis before age 30 were included.
- Next-generation sequencing (NGS) was used to analyze ABCB4, ABCB11, and ATP8B1 genes.
Main Results:
- 25% of patients (8/32) had ABCB4 mutations.
- 18% (3/17) had ATP8B1 variants and 6% (1/17) had ABCB11 variants.
- Mutations were identified in 44% of patients meeting LPAC criteria, versus 29% with symptom onset before 30 as the sole criterion.
Conclusions:
- LPAC should be systematically investigated in young adults with symptomatic cholelithiasis.
- Genetic testing for LPAC is recommended primarily for patients meeting established diagnostic criteria.
Background And Aims:
Low phospholipid-associated cholelithiasis syndrome (LPAC) is characterized by recurrent symptomatic cholelithiasis in young adults associated with ABCB4 gene mutations. Current diagnosing criteria are complex and heterogeneous, making this a largely underdiagnosed entity. Also, although recommended, genetic testing is not necessary for the diagnosis and its real advantages are not clear. The aim of our study was to explore the prevalence of ABCB4 mutations in symptomatic patients with cholelithiasis before the age of 30.
Methods:
We conducted a multicentric prospective cohort study including patients with symptomatic cholelithiasis presenting before 30 years of age in 4 Portuguese centres between January 2017 and December 2019. ABCB4 gene was analyzed by next generation sequencing (NGS) including all exons and flanking regions. In 17/32 patients ABCB11 and ATP8B1 variants were also analyzed by NGS.
Results:
Thirty-two patients were included (75% females, median age of symptom onset was 23 ± 5 years). We found that 8/32 (25%) patients had mutations in ABCB4 gene, 3/17 (18%) in ATP8B1 gene and 1/17 (6%) in ABCB11 gene. 44% (8/18) of patients with LPAC syndrome criteria had identified variants, while the prevalence of mutations in patients with symptoms onset before 30 as sole criteria was 29%.
Conclusion:
Our results suggest that LPAC should be systematically suspected and investigated in patients with symptomatic cholelithiasis before age of thirty, but genetic testing should only be attempted in patients complying with the more stringent LPAC criteria.
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