ALAGILLE SYNDROME
 
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    ALAGILLE SYNDROME

     

    DEFINITION:

    An autosomal dominant disorder resulting in a syndrome char acterized by hepatic and cardiac abnormalities.

    EPIDEMIOLOGY:

    • incidence: rare (over 100 cases world-wide)
    • age of onset:
      • infancy (jaundice)
    • risk factors:
      • familial - autosomal dominant and sporadic
        • chrom.#: 20p11.2
        • gene: ?
      • M = F

    PATHOGENESIS:

    1. Background

    • a disorder causing a direct hyperbilirubinemia and jaundice due to a persistent intrahepatic cholestasis

    2. Genetic Defect

    • genetic defect -> may be a defect in a specific connective tissue component present in the bile ducts, vasculature, and bone -> hepatic ductular hypoplasia -> intrahepatic cholestasis -> jaundice

    CLINICAL FEATURES:

    1. Gastrointestinal Manifestations

    1. Cholestasis

    • poor feeding, vomiting, lethargy, irritability (pruritis)
    • hepatomegaly +/- splenomegaly, steatorrhea, jaundice

    2. Complications

    • malabsorption of fats and fat-soluble vitamins (D,E,A,K)
    • failure to thrive
    • hepatic fibrosis with portal hypertension
    • cirrhosis with liver failure
    • hepatocellular carcinoma

    2. Cardiac Manifestations

    • 88% - peripheral pulmonary artery stenosis
    • 50% - atrial and ventricular defects
    • diffuse hypoplasia of the pulmonary artery

    3. Musculoskeletal Manifestations

    1. Facial

    • triangular-shaped facies, deeply set eyes
    • prominent forehead, bulbous tip of nose

    2. Digits

    • short distal phalanges
    • abnormally placed thumbs

    4. Other Manifestations

    1. Neurologic

    • hypoflexia or arreflexia
    • mild-moderate mental retardation
    • poor school performance

    2. Ophthalmologic

    • posterior embryotoxon (anterior chamber anomaly)
    • retinal pigmentary changes

    3. Endocrine

    • hypogonadism
    • rickets
    • short stature

    4. Renal

    • renal dysplasia
    • renal artery stenosis
    • hypertension

    INVESTIGATIONS:

    1. Serum

    • conjugated hyperbilirubinemia
    • elevated bile salts, cholesterol, AST, ALT, alkaline phosphatase
    • vitamin D,E,A,K deficiencies

    2. For Malabsorption

    • elevated 72 hour fecal fat content

    3. Biopsy

    1. Liver

    • hypoplasia of intrahepatic bile ducts

    4. Imaging Studies

    1. Skeletal X-Rays

    • butterfly vertebrae

    MANAGEMENT:

    1. Supportive

    • natural history one of decreasing bilirubin levels with age with improvement of cholestasis, i.e., benign condition
    • CVS and hepatic complications have been known to lead to death

     

 

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