Alagille Syndrome Treatment & Management

  • Author: Ann Scheimann, MD, MBA; Chief Editor: Carmen Cuffari, MD   more...
 
Updated: Feb 7, 2012
 

Medical Care

Treatment strategies include the following:

  • Correction of vitamin deficiencies with appropriate vitamin dosage is important for optimal growth and development in patients with Alagille syndrome (AS). Water miscible forms of vitamins A, D, E, and K frequently are poorly absorbed. Complexes of vitamins A, D, E, and K with polyethylene glycol compounds (TPGS) are generally well tolerated by patients and are better absorbed. Zinc deficiency is sometimes observed; zinc is easily replaced via oral compounds.
  • Some decreases in the degree of hyperlipidemia have been treated with cholestyramine.
  • Pruritus is often recalcitrant to medical therapy and significantly impacts on the quality of life. Trials of antihistamine agents, such as hydroxyzine and diphenhydramine, are helpful to some patients. Several studies have noted beneficial effects of either cholestyramine (12-15 g/d) or rifampin in management of bile acid-induced pruritus found in patients with Alagille syndrome.[14]
  • A cardiologist should manage cases of clinically significant cardiac disease.
  • All patients, except those with peripheral pulmonic stenosis, require subacute bacterial endocarditis (SBE) prophylaxis.
  • Screening for other vascular anomalies, such as aneurysms or stenoses, such be considered.
  • Administer standard immunizations along with the hepatitis A vaccine to patients with liver manifestations. Also administer the multivalent pneumococcal vaccine to these patients, particularly if ascites is present due to the risk for spontaneous bacterial peritonitis.
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Surgical Care

Surgical strategies include the following:

  • The exclusion of the diagnosis of extrahepatic biliary atresia (EHBA) via exploratory laparotomy and intraoperative cholangiography is not infrequent in patients with Alagille syndrome. Some studies have noted that 3-5% of patients undergoing the Kasai procedure for EHBA are eventually diagnosed with nonsyndromic bile duct paucity or Alagille syndrome.
  • Surgical management for bile acid–induced pruritus includes biliary diversion and eventual orthotopic liver transplantation for those with refractory disease.[15] Whitington et al reported a series of patients treated with partial external biliary diversion for pruritus associated with Alagille syndrome.[16] They noted a decrease in bile salt concentrations and some abatement of pruritus and xanthomas; however, the results for the patients with Alagille syndrome were less striking than with other preoperative diagnoses, including progressive familial intrahepatic cholestasis.
  • Indications for consideration of liver transplantation include the following:[17]
    • Progressive hepatic dysfunction
    • Severe portal hypertension
    • Failure to thrive
    • Intractable pruritus and osteodystrophy
  • Estimated 20-year survival rates are 80% for those not requiring liver transplantation and 60% for those requiring transplantation. Among children with cholestatic liver disease, 1-year and 5-year survival after liver transplantation is significantly lower in children with Alagille syndrome than in children with biliary atresia.[18]
  • Patients with more serious cardiovascular anomalies, including tetralogy of Fallot, ventricular septal defect (VSD) with pulmonary atresia (PA), atrial septal defect (ASD) and VSD, and patent ductus arteriosus (PDA), are likely to eventually require cardiac surgery. The 20-year predicted survival by Kaplan-Meier plots for those with significant intracardiac lesions is 40%; the 20-year predicted survival for those without intracardiac lesions is 80%.
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Consultations

Subspecialty consultation may facilitate diagnosis and provide long-term care.

  • Consultation with an ophthalmologist may provide the diagnosis.
  • A pediatric hepatologist can assist with management of chronic cholestatic liver disease.
  • Consultation with a cardiologist can assist with the diagnosis of Alagille syndrome and therapy for intracardiac disease, as well as other vascular abnormalities.
  • Consultation with a nephrologist is indicated if significant structural renal disease is present or if suspicions of evolving renal insufficiency arise.
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Diet

Dietary considerations may include the following:

  • Diets higher in carbohydrates and medium chain triglycerides are generally absorbed better in patients with Alagille syndrome.
  • Consider drip feeds via nasogastric tube or gastrostomy in patients with poor weight gain and increased caloric requirements secondary to malabsorption and cholestasis or cardiac disease.
  • Patients with Alagille syndrome and cholestasis may develop essential fatty acid deficiency if not appropriately supplemented.
  • Supplementation of fat-soluble vitamins is necessary.
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Activity

Activity is not limited unless patient also has significant intracardiac disease.

Patients with evidence of hypersplenism should avoid contact sports.

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Contributor Information and Disclosures
Author

Ann Scheimann, MD, MBA  Associate Professor, Department of Pediatrics, Section of Nutrition and Gastroenterology, Baylor College of Medicine and Johns Hopkins Medical Institution

Ann Scheimann, MD, MBA is a member of the following medical societies: North American Society for Pediatric Gastroenterology and Nutrition

Disclosure: Nothing to disclose.

Specialty Editor Board

Robert Baldassano, MD  Director, Center for Pediatric Inflammatory Bowel Disease, Children's Hospital of Philadelphia; Professor, Department of Pediatrics, Division of Gastroenterology and Nutrition, University of Pennsylvania School of Medicine

Robert Baldassano, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Gastroenterological Association, and North American Society for Pediatric Gastroenterology and Nutrition

Disclosure: Abbott, Inc Consulting fee Consulting

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Steven M Schwarz, MD, FAAP, FACN, AGAF  Professor of Pediatrics, Children's Hospital at Downstate, State University of New York Downstate Medical Center

Steven M Schwarz, MD, FAAP, FACN, AGAF is a member of the following medical societies: American Academy of Pediatrics, American College of Nutrition, American College of Physician Executives, American Gastroenterological Association, American Pediatric Society, Gastroenterology Research Group, New York Academy of Medicine, North American Society for Pediatric Gastroenterology and Nutrition, and Society for Pediatric Research

Disclosure: Curemark, LLC Consulting fee Board membership; Centocor, Inc. Grant/research funds Independent contractor; Johnson & Johnson, Inc. Grant/research funds Independent contractor

Chief Editor

Carmen Cuffari, MD  Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns Hopkins University School of Medicine

Carmen Cuffari, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, and Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

References

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  2. Watson GH, Miller V. Arteriohepatic dysplasia: familial pulmonary arterial stenosis with neonatal liver disease. Arch Dis Child. Jun 1973;48(6):459-66. [Medline].

  3. Alagille D, Odievre M, Gautier M, Dommergues JP. Hepatic ductular hypoplasia associated with characteristic facies, vertebral malformations, retarded physical, mental, and sexual development, and cardiac murmur. J Pediatr. Jan 1975;86(1):63-71. [Medline].

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  16. Whitington PF, Whitington GL. Partial external diversion of bile for the treatment of intractable pruritus associated with intrahepatic cholestasis. Gastroenterology. Jul 1988;95(1):130-6. [Medline].

  17. [Guideline] Murray KF, Carithers RL Jr. AASLD practice guidelines: Evaluation of the patient for liver transplantation. Hepatology. Jun 2005;41(6):1407-32. [Medline]. [Full Text].

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Typical facial features of Alagille syndrome. Note broad forehead, deep-set eyes and pointed chin.
 
 
 
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