HISTORY:

One month old boy with jaundice and hyperbilirubinemia.

DISCUSSION:

Alagille syndrome is an autosomal dominant disorder with abnormalities of the liver, heart, skeleton, eye, kidneys, and characteristic facial appearance.  Alagille et al described several patients with these features and there was an association with hypoplasia of the hepatic ducts.  Incidence in the United States is approximately 1 in every 100,000 live births. There is no difference in penetrance with regard to gender.  Most children are evaluated prior to 6 months for either neonatal jaundice or cardiac murmurs.  Morbidity arises from bile duct paucity or cholestatic liver disease, underlying cardiac disease, and renal disease.

Hepatic disease is a key feature of Alagille syndrome, with most infants presenting with cholestatic jaundice.  Liver biopsy often reveals a paucity of intrahepatic bile ducts, which was noticed in this patient.  Most patients will have cardiac murmurs.  Skeletal abnormalities involve the vertebrae, ribs, and hands.  Commonly associated facial features include broadened forehead, pointed chin, and elongated nose with bulbous tip.  Children frequently have diminished linear growth and may have mild developmental delay, some of which may be associated with vitamin deficiencies.  Renal presentation may include renal artery stenosis, lipoid nephrosis, or glomerulosclerosis may present with signs and symptoms of chronic hypertension.

Treatment includes management of nutritional deficiencies, standard immunizations, as well as close cardiology follow-up.  Symptomatic control of pruritus may be achieved with anti-histamines.  Liver transplantation may be considered with progressive hepatic dysfunction, severe portal hypertension, failure to thrive, as well as intractable pruritus and osteodystrophy.