S2487 A Tale of Two Sydromes: A Unique Case of Crigler-Najjar in a Young Male

Abstract

INTRODUCTION: Crigler-Najjar Syndrome (CNS) is an uncommon genetic disorder that is characterized by non-hemolytic unconjugated hyperbilirubinemia and is divided into types I and II. CNS II has much overlap with Gilbert's syndrome, another hereditary defect in bilirubin metabolism. Though these syndromes share similar presentations, diagnosis through careful history taking and performing early genetic analysis can aid in prompt diagnosis and reduce extraneous testing. Our case describes a young man who was diagnosed with CNS type II via genetic analysis after years of misdiagnosis. CASE DESCRIPTION/METHODS: An 18-year-old male presented to the hospital with jaundice. Labs revealed mild elevation of liver enzymes, total bilirubin of 19.7 mg/dL and direct bilirubin of 4.2 mg/dL. CT abdomen and pelvis showed mild hepatomegaly without biliary duct dilatation. Hemolysis labs including LDH and haptoglobin were normal. The patient underwent plasmapheresis and started on phenobarbital 60 mg three times a day. Repeat labs two weeks later showed improvement in bilirubin levels to 9.5 mg/dL. Further history revealed that the patient had a longstanding history of jaundice and elevated bilirubin levels since childhood. Due to persistently elevated bilirubin levels despite phenobarbital therapy, genetic testing was performed which revealed a homozygous mutation of the UGT1A1 gene which confirmed CNS type II. The patient continued to have monthly phototherapy treatments with an improvement in symptoms. DISCUSSION: CNS is a disorder in which there is a mutation in the UGT1A1 gene which is needed for bilirubin conjugation. CNS type I is fatal in infancy and CNS type II often presents with persistent jaundice. CNS type II is often confused with Gilbert's disease as both cause the same overlap of symptoms which are exacerbated by stress or illness. Our patient was initially diagnosed with Gilbert's as his symptoms occurred intermittently and bilirubin levels fell after previous treatments. A key difference is that in Gilbert's disease, total bilirubin levels rarely reach higher than 6 mg/dl and typically normalize after treatment. In contrast, in CNS type II, plasma exchange or phenobarbital cause bilirubin levels to drop by at least 25% however levels rarely normalize. In our patient, a key clinical indicator for CNS type II was the high bilirubin levels without drop to normal which should be used to differentiate between each syndrome.