Alagille Syndrome Follow-up

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

Further Inpatient Care

Patients may require inpatient treatment for nutritional support, cardiovascular disease, and chronic liver disease.

  • Patients with evidence of undernutrition and failure of conservative measures may benefit from gastrostomy placement for initiation of nocturnal drip feedings.
  • Patients may require cardiac catheterization and cardiac or vascular surgery/procedures for significant symptomatic lesions.
  • Complications of chronic liver disease, including variceal hemorrhage, refractory ascites, and spontaneous bacterial peritonitis (as well as development of hepatocellular carcinoma), occur in patients with Alagille syndrome and long-standing liver involvement. These patients merit strong consideration for liver transplantation.
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Further Outpatient Care

Further care may include the following:

  • Monitor patient's nutritional status. Screen patients for fat-soluble vitamin deficiencies.
  • Consultation with a pediatric cardiologist for management of structural cardiac or vascular disease, and hyperlipidemia is advised.
  • Manage chronic cholestatic liver disease, including pruritus, cirrhosis and portal hypertension, ascites, and screening for hepatocellular carcinoma, when appropriate.
  • Manage chronic renal disease.
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Transfer

Patients with Alagille syndrome and significant cardiovascular or hepatic disease merit consultation with a subspecialist.

Consider transferring patient if signs of decompensation are evident upon presentation or if they are likely to evolve during hospitalization; patient also must be stable for transfer.

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Deterrence/Prevention

Patients with significant intracardiac disease require subacute bacterial endocarditis (SBE) prophylaxis. Consider trials of bile acid-binding resins (eg, cholestyramine) to those with significant hyperlipidemia and pruritus.

Supplementation of fat-soluble vitamins, alteration in dietary intake (higher carbohydrate/medium chain triglyceride), and immunizations (hepatitis B, hepatitis A, Pneumovax) may minimize the development of complications of cholestatic chronic liver disease.

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Complications

The following complications are possible:

  • Hepatic complications arise from cholestasis and cirrhosis. Infants may present with neonatal jaundice. Jaundice resolves by age 2 years or cholestasis persists. Unrecognized deficiencies of fat-soluble vitamins (A, D, E, K) can contribute to morbidity (eg, osteopenia, hemolytic anemia) and mortality (eg, intracranial hemorrhage, aberrant intracerebral vessels secondary to abnormal notch or JAG1 expression) from bleeding events. Severe intractable pruritus occurs in many children with Alagille syndrome, prompting consideration for liver transplantation. Several patients have developed hepatocellular carcinoma in early adulthood.
  • Major contributors to morbidity arise from bile duct paucity or cholestatic liver disease, underlying cardiac disease, and renal disease.
  • Structural cardiac disease and hyperlipidemia or atherosclerosis contribute to morbidity and mortality of Alagille syndrome. Cardiac murmurs are noted in fewer than 95% of patients. Structural anomalies associated with Alagille syndrome range from mild peripheral pulmonic stenosis to severe tetralogy of Fallot. Aneurysms and stenotic lesions have been described within the arterial system (eg, carotids, aorta, renal), as has the development of changes similar to Moyamoya disease. Hyperlipidemia commonly is manifested as xanthomas. Patients have high levels of plasma cholesterol, low-density lipoprotein (LDL), and apoprotein B, predisposing to the development of atherosclerosis.
  • Structural renal disease as well as glomerulosclerosis and nephrosclerosis have been described in patients with Alagille syndrome. Renal anomalies include renal artery stenosis, ectopic kidney, single kidney, and ureteral duplications. The development of glomerulosclerosis in patients with Alagille syndrome has been attributed to hypercholesterolemia and lecithin cholesterol acyltransferase (LCAT) deficiency, as well as stimulation of excessive production of extracellular matrix. One patient has been reported to require renal transplantation.
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Prognosis

Cardiac disease and liver disease can significantly impact the life expectancy of patients with Alagille syndrome; presence of hepatic disease also alters life expectancy.

Patients with more significant cardiovascular anomalies (tetralogy of Fallot, pulmonary atresia [PA] with ventricular septal defect [VSD], atrial septal defect [ASD]/VSD, patent ductus arteriosus [PDA]) eventually require cardiac surgery. The 20-year predicted survival rate via Kaplan-Meier plots for individuals with significant intracardiac lesions is 40%; for those individuals without significant intracardiac lesions, the survival rate is 80%.

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Patient Education

For excellent patient education resources, visit eMedicine's Heart Center and Cholesterol Center. Also, see eMedicine's patient education articles Tetralogy of Fallot, High Cholesterol, and Cholesterol FAQs.

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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.

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