PEDBASE.org - The Pediatric Database - Detailed information of 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

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