Patients with Alagille syndrome have a higher risk of having a lower IQ, while those with alpha-1 antitrypsin deficiency (AATD) and intrahepatic cholestasis do not. Moreover, patients with Alagille syndrome and those with AATD appear to be vulnerable to deficits in working memory and processing speed, which suggests they may have attention/executive function impairment.

These are the findings of a new study published in the Journal of Pediatric Gastroenterology and Nutrition

“Malnutrition, liver disease severity, and sociodemographic factors appear related to [full-scale IQ] deficits,” first author Daniel H. Leung, MD, from the Division of Pediatric Gastroenterology, Hepatology and Nutrition at Texas Children’s Hospital, Baylor College of Medicine, in Houston, Texas, and the coauthors of the study wrote. They concluded that these could, therefore, be potential targets of early intervention. 

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The aim of the researchers was to evaluate the neurodevelopmental status of children with inherited cholestatic liver diseases. They analyzed patients with Alagille syndrome, progressive familial intrahepatic cholestasis, and AATD who enrolled in a longitudinal, multicenter study and completed 2 intelligence tests. The full-scale IQs of the participants were analyzed continuously and categorically during the study. 

The results showed that the mean full-scale IQ was lower in patients with Alagille syndrome than in those with AATD. 

The frequency of a full-scale IQ lower than 85 was highest among patients with Alagille syndrome and was greater than expected based on normal distribution.

Moreover, patients with Alagille syndrome scored significantly lower than test norms in almost all Wechsler Preschool and Primary Scale of Intelligence-III composites. 

On the other hand, patients with AATD scored lower on working memory and processing speed, and the scores of patients with progressive familial intrahepatic cholestasis were not different from test norms. 

The researchers found that factors that were associated with IQ included total bilirubin, alkaline phosphatase, albumin, hemoglobin, and parental education.


Leung DH, Sorensen LG, Ye W, et al.; Childhood Liver Disease Research Network (ChiLDReN). Neurodevelopmental outcomes in children with inherited liver disease and native liver. J Pediatr Gastroenterol Nutr. Published online October 22, 2021. doi:10.1097/MPG.0000000000003337