BYLER DISEASE

 

BYLER DISEASE

 

DEFINITION:

A disorder of hepatic bile formation resulting in chronic, progressive cholestasis and eventually cirrhosis.

EPIDEMIOLOGY:

  • incidence: rare (about 75 cases reported)
  • age of onset:
    • first year of life
  • risk factors:
    • familial - autosomal recessive
      • chrom.#: ?
      • gene: ?
    • M = F
    • Amish, Greenland Eskimos

PATHOGENESIS:

1. Background

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

2. Genetic Defect

  • genetic defect -> defect in hepatic bile formation -> reduced bile flow (cholestasis) and retention of bile products -> retained bile salts cause hepatomegaly, elevated transaminases, hepatic fibrosis and eventually cirrhosis

CLINICAL FEATURES:

1. Gastrointestinal Manifestations

1. Cholestasis

  • anorexia/poor feeding - nausea/vomiting
  • fatigue/lethargy - pruritis/irritability
  • hepatomegaly +/- splenomegaly - steatorrhea
  • jaundice
  • unremitting leading to progressive biliary cirrhosis

2. Complications

  • malabsorption of fats and fat-soluble vitamins (D,E,A,K)
  • failure to thrive
  • cholecystolithiasis
  • hepatic fibrosis with portal hypertension
  • cirrhosis (after 5-10 years) with liver failure
  • hepatocellular carcinoma

INVESTIGATIONS:

1. Serum

  • conjugated hyperbilirubinemia
  • elevated bile salts, cholesterol, AST, ALT, alkaline phosphatase
  • low gamma-glutamyl transpeptidase
  • vitamin D,E,A,K deficiencies

2. For Malabsorption

  • elevated 72 hour fecal fat content

3. Biopsy

1. Liver

  • cellular and canalicular cholestasis, lobular disarray, giant cell transformation, hepatocyte necrosis - cirrhosis - micronodular biliary cirrhosis with marked pseudoductular proliferation

MANAGEMENT:

1. Medical

1. Symptomatic

  • cholestyramine to reduce bile salt concentration and pruritis
  • supplementation with fat-soluble vitamins (D,E,A,K)
  • promote bile flow with phenobarbital or rifampin

2. Surgical

  • liver transplantation for cirrhosis

3. Prognosis

  • death due to hepatic failure or hepatocellular carcinoma in the first or second decade unless transplanted

 

 

 

Pediatric Database - BYLER DISEASE

Pediatric Organization - Pedbase [at] Gmail.com