Related Experiment Video
Updated: Oct 15, 2025
09:54
Lentiviral Vector-mediated Gene Therapy of Hepatocytes Ex Vivo for Autologous Transplantation in Swine
Published on: November 4, 2018
8.3K
Neurodevelopmental Outcomes in Children With Inherited Liver Disease and Native Liver
Daniel H Leung1, Lisa G Sorensen2, Wen Ye3
1Division of Pediatric Gastroenterology, Hepatology and Nutrition, Texas Children's Hospital, Baylor College of Medicine, Houston, TX.
Journal of Pediatric Gastroenterology and Nutrition
|October 25, 2021
Summary
Children with Alagille syndrome (ALGS) face higher risks of lower intelligence, while progressive familial intrahepatic cholestasis (PFIC) and alpha-1 antitrypsin deficiency (A1AT) do not show this trend. Liver disease severity and malnutrition impact cognitive outcomes.
Area of Science:
- Pediatric Hepatology
- Neurodevelopmental Pediatrics
- Genetics
Background:
- Inherited cholestatic liver diseases, including Alagille syndrome (ALGS), progressive familial intrahepatic cholestasis (PFIC), and alpha-1 antitrypsin deficiency (A1AT), can impact overall child development.
- Evaluating neurodevelopmental status is crucial for understanding the long-term health implications of these conditions.
Purpose of the Study:
- To assess the neurodevelopmental status of children with ALGS, PFIC, and A1AT, focusing on Full Scale Intelligence Quotient (FSIQ).
- To identify variables that predict cognitive impairment in these pediatric liver disease populations.
Main Methods:
- A longitudinal, multicenter study involving 215 children diagnosed with ALGS, PFIC, or A1AT.
- Neurodevelopmental status was evaluated using the Wechsler Preschool and Primary Scale of Intelligence-III or Intelligence Scale for Children-IV.
- Statistical analyses included univariate linear regression to identify risk factors associated with FSIQ, stratified by disease.
Main Results:
- Children with ALGS had a significantly lower mean FSIQ (94) compared to those with A1AT (101).
- The frequency of FSIQ below 85 was highest in ALGS (29%), exceeding expected rates.
- ALGS patients showed deficits across most cognitive domains, while A1AT patients exhibited impairments in working memory and processing speed. PFIC patients did not differ from norms.
- Total bilirubin, alkaline phosphatase, albumin, hemoglobin, and parental education were significantly associated with FSIQ.
Conclusions:
- ALGS is associated with an increased risk of lower FSIQ, unlike A1AT and PFIC.
- Working memory and processing speed deficits in ALGS and A1AT suggest potential attention/executive function impairments.
- Malnutrition, liver disease severity, and sociodemographic factors are linked to FSIQ deficits, highlighting potential targets for early intervention.
More Related Videos
Related Concept Videos
01:22Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test
24
In clinical practice, the direct measurement of hepatic blood flow to evaluate liver function presents significant challenges due to the intricate and specialized nature of the necessary techniques. Consequently, healthcare professionals often rely on empirical estimates derived from thorough patient examinations and liver function tests to gauge liver health. Among the tools at their disposal, the Child–Pugh and MELD scoring systems stand out for their ability to categorize and assess...
24
01:26Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow
23
Chronic liver disease significantly impacts drug metabolism due to alterations in hepatic blood flow and enzyme accessibility. This disruption affects the body's pharmacokinetics—the movement and processing of drugs within the system. Key enzymes crucial for metabolizing medications become less accessible, changing how drugs are processed and utilized. Furthermore, liver disease influences the synthesis of plasma proteins, such as albumin and globulins, which play critical roles in drug...
23
01:26Diseases of the Liver and Gallbladder
1.4K
Liver and gallbladder diseases are a significant health concern, with prominent conditions including cirrhosis, hepatitis, non-alcoholic fatty liver disease (NAFLD), and gallstones. Jaundice is a common manifestation of liver and biliary disease.
Cirrhosis is characterized by the scarring of hepatic lobules in the liver, which are replaced by fibrous tissue, affecting the liver's normal functioning. NAFLD, on the other hand, is caused by an excessive build-up of fat in the liver, not...
Cirrhosis is characterized by the scarring of hepatic lobules in the liver, which are replaced by fibrous tissue, affecting the liver's normal functioning. NAFLD, on the other hand, is caused by an excessive build-up of fat in the liver, not...
1.4K
01:24Pharmacokinetics in Pediatric Patients: Drug Metabolism
33
In pediatric care, understanding the nuances of hepatic drug metabolism is crucial, as it significantly differs from that of adults. This divergence is primarily due to the developmental stage of drug-metabolizing enzymes, which affects how medications are processed in the body. In neonates, for instance, the activity of Phase I enzymes—critical for the initial breakdown of drugs—is markedly reduced, functioning at just 20–40% of the levels seen in adults. This reduction poses...
33
01:08Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment
25
Hepatic impairment, characterized by decreased liver function, does not uniformly mandate adjustments in drug dosage. Whether dosage modifications are necessary depends on various factors related to the drug's metabolism and elimination pathways. If a drug is primarily excreted via the kidneys and bypasses significant hepatic processing, if it undergoes minimal metabolic transformation in the liver, or if it is volatile and primarily expelled through the lungs, dose adjustments may not be...
25
01:20Inborn Errors of Metabolism
331
Phenylketonuria (PKU) is a protein metabolism disorder characterized by high blood levels of the amino acid phenylalanine. This results from a mutation in the gene responsible for phenylalanine hydroxylase, an enzyme that converts phenylalanine into tyrosine. When this enzyme is deficient, phenylalanine builds up in the blood, leading to symptoms such as vomiting, rashes, seizures, growth deficiency, and severe mental retardation. An early diagnosis and a diet restricting phenylalanine intake...
331