An Unusual Cause of Jaundice: Cholestasis-lymphedema Syndrome “Aagenaes Syndrome”: ACG/AstraZeneca Clinical Vignette Award: Presidential Poster

Abstract

Purpose: A 61-year-old Caucasian male of Norwegian descent presented to the emergency department with complaints of progressive jaundice, pruritus, dark urine, clay-colored stools, and lower extremity edema for one month. This patient had history of intermittent jaundice all of his life, with chronic lower extremity edema. As an infant, he had an exploratory laparotomy for biliary atresia, but no definitive intervention was done. There was no family history of liver disease, no history of alcohol use, and his only medication was furosemide. On examination, he had no stigmata of chronic liver disease, reduced air entry in both lower lung fields, a healed laparotomy scar, and 2 + bilateral pedal edema. Initial labs showed a normal complete blood count and renal function, but a total bilirubin of 6.7 (Direct 4.2), alkaline phosphatase of 422 with AST 41, and ALT 32. A chest X-ray done in the ED revealed bilateral pleural effusions. Subsequent work-up for chronic liver disease was negative, and liver ultrasound with Dopplers and MRI of the liver were negative. A liver biopsy showed chronic lymphocytosis. Thoracentesis demonstrated chylothorax with triglycerides of 815 mg/dl. In summary, this is a 61 year-old Caucasian male of Norwegian heritage with recurrent, intermittent, cholestatic jaundice with chronic lymphedema, pruritus, and chylothorax. Given this constellation of findings, we diagnosed our patient with Aagenaes syndrome. This syndrome was first described in six large Norwegian families, and is characterized by chronic lymphedema and cholestasis. Its inheritance is autosomal recessive, with a prevalence of < 1 in 100,000. Pathogenesis involves a defect in lymphangiogenesis with generalized hypoplasia of lymphatics and the abnormal development of lymphatics around small biliary tracts. Patients present with severe neonatal cholestasis, which decreases during early childhood and becomes episodic later. Lymphedema is present at birth, but is usually noticed later, and affects the small bowel and thoracic soft tissue leading to chylothorax. Liver histology may show non-specific inflammation (as in our patient), giant cell transformation, fibrosis, or cirrhosis. Prognosis for liver disease is good. Management involves eating a fat-reduced diet during cholestasis, with supplementation of fat-soluble vitamins. We used subcutaneous octreotide for the chylothorax, with resolution of his pleural effusions. The patient is doing well currently, and is being followed in the hepatology clinic.