[Infantile cholestasis caused by CFTR mutation: case report and literature review]
1Department of Pediatrics, Jinshan Hospital Affiliated to Fudan University, Shanghai 201508, China.
Insights
Cystic fibrosis (CF) should be considered in infants with cholestasis, especially those with meconium ileus or delayed meconium passage. Genetic analysis confirms CFTR mutations, and ursodeoxycholic acid (UDCA) may improve liver function.
Area of Science:
- Pediatrics
- Medical Genetics
- Hepatology
Background:
- Infantile cholestasis can present with diverse etiologies, necessitating comprehensive diagnostic approaches.
- Cystic fibrosis, a genetic disorder, is increasingly recognized as a cause of cholestatic liver disease in infants.
Observation:
- A case study highlights an infant with neonatal cholestasis, delayed meconium, and confirmed compound heterozygous CFTR mutations.
- Literature review identified 25 infantile cholestatic cases linked to cystic fibrosis, often presenting with meconium ileus or delayed passage.
Findings:
- CFTR gene mutations are associated with infantile cholestasis, characterized by direct hyperbilirubinemia and elevated liver enzymes.
- Ursodeoxycholic acid (UDCA) treatment was associated with normalized liver function in the case study and improved outcomes in reviewed literature.
- Mortality in CF-related cholestasis was observed in patients not receiving UDCA, with causes including persistent cholestasis and respiratory failure.
Implications:
- Early consideration of cystic fibrosis in infants with cholestasis and gastrointestinal symptoms is crucial for timely diagnosis.
- Genetic testing for CFTR mutations should be part of the workup for unexplained infantile cholestasis.
- UDCA may serve as a beneficial therapeutic agent in managing liver dysfunction associated with CFTR mutations in infants.
Abstract:
Objective: To study the clinical presentation, biochemical features and genetic analysis of an infant with cholestasis related to the CFTR mutations. Method: The clinical presentation, laboratory investigations and management of a case with infantile cholestasis caused by CFTR mutations were summarized and the relevant literature was reviewed. Result: (1) The patient was a 5 months old boy with cholestasis which developed in neonatal period with delayed meconium exclusion.The laparoscopic exploration was performed to exclude biliary atresia because of acholic stool when he was two months old.Ursodeoxycholic acid (UDCA), cholestyramine and phenobarbital treatment was applied.The genetic analysis showed compound heterozygous mutations in CFTR. The liver function normalized when he was 11 months old.When he was 21 months old, he had normal appearance except mild splenomegaly.(2) Literatures review identified 25 infantile cholestatic cases related to cystic fibrosis (CF) diagnosed by sweat test or gene analysis.Delayed meconium passage was found in five, meconium ileus in six cases.The liver function tests characterized by the direct hyperbilirubinemia with elevated transaminase, glutamyltranspeptidase and alkaline phosphatase levels.Genetic analysis revealed eight homozygotes of delF508, four heterozygotes of delF508 and one compound heterozygotes of c. 263T>G/ c. 2089-2090ins in CFTR.Jaundice resolved in 20 patients, ten of them were prescribed oral ursodesoxycholic acid (15-20 mg/(kg·d)). Five patients died, none of them received oral UDCA.Two of them had persisted cholestatic until death. Among the other three dead, two died from respiratory failure and one from cardiopulmonary failure. Conclusion: Cystic fibrosis should be considered in cholestatic infants with meconium ileus or delayed meconium passage.Genetic analysis could confirm the diagnosis.UDCA may be beneficial to improve the liver function.
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