Normal cholestanol in a genetically confirmed cerebrotendious xanthomatosis case presenting as neonatal jaundice

Cerebrotendinous xanthomatosis (CTX) is a treatable genetic disorder associated with deficiency of the sterol 27-hydroxylase enzyme (CYP27A1), important in bile acid synthesis. CTX may present in the newborn period as hepatic jaundice/cholestasis, that can resolve or can progress to fatal liver disease. Many cholestasis gene panel tests now include CYP27A1. For infants presenting with cholestasis that are identified to have CTX, follow-up biochemical testing is recommended. Here, we describe a case of an infant with neonatal jaundice genetically diagnosed with CTX through the use of cholestasis gene panel testing. Follow-up biochemical testing determined the infant had normal plasma cholestanol, inconsistent with a diagnosis of CTX according to expert guidance. We report that quantitative biochemical testing for bile acid precursors and bile alcohols provided definitive biochemical evidence of CTX and recommend that such testing is advised in infants with CYP27A1 gene analysis indicative of CTX.