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248 A longterm follow-up of two siblings with alagille syndrome
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  1. Matea Crnković Ćuk,
  2. Barbara Perše,
  3. Petra Matijević,
  4. Orjena Žaja
  1. Department of Pediatrics, Sestre milosrdnice University Hospital Center

Abstract

Alagille syndrome (AGS) is a rare genetic disorder inherited in autosomal dominant pattern that affects the liver, heart, and other organ systems. Major feature of AGS is liver damage caused by paucity of the bile ducts which leads to chronic cholestasis marked by jaundice, pruritus, xanthomas and sometimes cirrhosis. Common associated anomalies include cardiac anomalies (peripheral pulmonary stenosis), butterfly vertebrae, posterior embryotoxon, dysmorphic facies and renal dysplasia.

We present a long-term follow up of two siblings aged 13 and 7 year diagnosed with AGS during infancy.

The older sibling, female, presented at 7 weeks with jaundice and history of acholic stools and dark urine. Laboratory tests confirmed cholestasis with elevated liver enzymes, bile acids, alpha-feto-protein and 5’-nucleotidase.

Hepatic scintigraphy confirmed severe intrahepatic cholestasis.

Ursodeoxicolic acid (UDCA) and phenobarbitone were introduced. Due to dysmorphic facial features (prominent forehead, broad nasal bridge, triangular facies and deep set eyes) AGS was suspected and confirmed by further evaluation (peripheral pulmonary stenosis and posterior embryotoxon). At 3 years old liver biopsy revealed paucity of bile ducts, changes typical to AGS, which definitely confirmed the diagnosis.

When the younger, male, sibling presented with typical phenotype and intrahepatic cholestasis in the neonatal period, AGS was immediately suspected. Of associated anomalies, peripheral pulmonary stenosis, posterior embryotoxon and butterflyvertebrae were all present. Stomatology exam revealed hypodontia in both siblings. Brain MRI conducted at age 3 revealed signs of hepatic encephalopaty with no associated vascular anomalies.

Both siblings had severe cholestatic liver disease in preschool period which had stabilized by school age with conservative treatment for pruritus and malabsorption. Both had severe hypercholesterolemia, in the younger sibling it was extreme with LDL cholesterol levels reaching up to 30,1 mmol/L? The levels of bile acids were also extremely high, reaching a maximum of 634,4 umol/L in the younger sibling. Therapy included chronic use of UDCA, liposoluble vitamins and MCT with a hypercaloric diet.

The natural evolution of the disease is favorable if liver transplantation is avoided until reaching school age. In both our patients, despite severe liver disease, psychosomatic development and quality of life remained intact.

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