Dr. Ira Shah
M.D, DNB, DCH(Gold Medalist), FCPS

Keywords : Arteriohepatic dysplasia , chronic cholestasis, pulmonary artery hypoplasia

Alagille first described a syndrome consistency of a paucity of interlobular bile ducts with chronic cholestasis. Patients with this syndrome typically have the following major features: peculiar facies, chronic cholestasis, butterfly-like vertebral arch defects, and peripheral pulmonary artery hypoplasia or stenosis; either isolated or associated with complex cardiovascular abnormalities. Patients typically present with conjugated hyperbilirubinemia due to chronic cholestasis within the first 3 months of life. Hepatomegaly and spleenomegaly are almost invariably present. A remarkable feature is the extreme degree of pruritis. Other less frequent features include growth retardation, mental retardation, renal disturbances, other vascular malformations, high pitched voice and delayed puberty with hypogonadism(1). This syndrome is extremely rare with very few patients reported in literature. We would like to present one such patient who presented to us.

18 month old male child BONCM to normal parents presented with jaundice since 2 months of age, clay colored stools with high colored urine, ½and pruritis since l year. Patient was noticed to have cyanosis, which increased, on crying. He had dysmorphic features in form of deep-seated eyes, with prominent forehead and small pointed chin. Patient had hepatomegaly with 5cm palpable liver. He also had an ejection systolic murmur with soft and single second heart sound suggestive of tetralogy of fallot physiology. Patient was clinically diagnosed as a case of Arteriohepatic dysplasia or Alagille syndrome. 2 D echo showed subvalvalar pulmonary stenosis with left pulmonary artery not seen. USG Abdomen was suggestive of gall bladder sludge with hepatomegaly. His liver enzymes were elevated. There was hyperbilirubinemia with increased direct compound (2.4mg% D= 1.2 mg%). Serum cholesterol (316 mg%) and Triglyceride (352 mg%) were markedly elevated. Liver scan (HIDA) showed decreased excretion. Patient was advised cardiac catheterisation to assess the anatomical malformation and evaluate further treatment. Liver biopsy was not undertaken in this patient. He was treated with fat soluble vitamins, cholestyramine, ureodeoxycholic acid. His pruritis markedly subsided with above management. He was started on T. Propranalol for his cyanotic heart disease and discharged. He was advised surgery for heart disease and option for liver transplantation was explained.

Alagille syndrome is an autosomal dominant disorder also referred to as Alagille- Watson syndrome, syndromic bile duct paucity and arteriohepatic dysplasia. It is a significant cause of neonatal jaundice in older children(2). It is characterized by 5 main characteristics (a) typical peculiar facies – prominent forehead, moderate hypertelorism with deep – set eyes, small pointed chin, and a saddle nose (b) chronic cholestasis (c) butterfly- like vertebral arch defects (seen in 80% of patients)(d) cardiovascular malformations- hypoplasia of pulmonary vascular tree, tetralogy of fallot etc and (e) posterior embryotoxon. (seen in 89% of patients)(3).

The course is characterized by recurrent episodes of cholestasis. The long- term prognosis is related to the severity and duration of early cholestasis, severity of complex cardiovascular abnormalities and the severity of liver disease and its associated portal hypertension.(1)

Liver biopsy shows absence of bile ducts from most portal triads.(1)

Genetic analysis have now shown that it arises from mutation of the JAGI gene located on chromosome 20, which encodes a ligand for Notch receptors(4).

Treatment is supportive with low fat diet, fat soluble vitamin supplements especially vitamin A and E. They also require phenobarbital and cholestyramine for cholestasis. For progressive disease, liver transplantation may be required.(1)

The 20 year predicted life expectancy is 75% for all patients, 80% for those not requiring transplantation and 60% for those requiring liver transplantation(5)