Neurodevelopmental Deficits in Children With Inherited Cholestatic Liver Disorders

Illustration of a girls liver.
Researchers evaluated the neurodevelopmental status of children with inherited cholestatic liver diseases and identified predictors of abnormal development.

Neurodevelopmental deficits in children with inherited cholestatic liver disorders and native liver appear to be greatest among those with Alagille syndrome (ALGS), according to a prospective multi-center study published in the Journal of Pediatric Gastroenterology and Nutrition.

ALGS, progressive familial intrahepatic cholestasis (PFIC), and alpha-1 antitrypsin deficiency (A1AT) are the most common inherited cholestatic liver disorders in children. Whether some liver disorders have more neurodevelopmental impairments than others is unknown. Therefore, researchers evaluated the neurodevelopmental status of children with inherited cholestatic liver diseases with native liver in a longitudinal study ( Identifier: NCT00571272).

In total, 215 children aged 3 to 16 years with ALGS (n=70), PFIC (n=43), and A1AT (n=102) completed the Wechsler Preschool and Primary Scale of Intelligence-III or Intelligence Scale for Children-IV, and a Full Scale Intelligence Quotient (FSIQ). FSIQ scores were analyzed continuously and categorically in order to study the association between scores and individual disease risk factors.

Mean patient age was 8.2 (SD, 3.8) years. Children with A1AT deficiency were more likely to be boys, while children with PFIC tended to be older.

The researchers found that children with ALGS had a lower mean FSIQ compared against children with A1AT (94 vs 101; P =.01). The frequency of FSIQ scores <85 (>1 SD below average) was also highest in children with ALGS (29%) compared against children with PFIC (18.6%) and those with A1AT deficiency (12.8%). Frequency of FSIQ scores <85 were also greater than expected in children with ALGS based on normal distribution (29% vs 15.9%; P =.003).

Children with ALGS scored significantly lower than test norms in almost all Wechsler composites, while children with A1AT deficiency scored lower on Working Memory and Processing Speed indices; children with PFIC did not differ from the test norms.

Total bilirubin, alkaline phosphatase, albumin, hemoglobin, and parental education were found to be significantly associated with FSIQ.

This study was limited by a lower than anticipated proportion of patients completing intelligence quotient testing. Additionally, disease subgroups were small and the overall patient cohort was predominantly boys, limiting analysis.

The authors concluded, “Early screening for and identification of neurodevelopmental deficits in children with ALGS should prompt therapies that can maximize developmental outcomes.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Leung DH, Sorensen LG, Ye W, et al, for the Childhood Liver Disease Research Network (ChiLDReN). Neurodevelopmental outcomes in children with inherited liver disease and native liver. JPGN. 2022;74(1):96-103. doi: 10.1097/MPG.0000000000003337