Deficit di sintesi degli acidi biliari tipo 2: un caso di colestasi in un lattante con GT basse

The paper reports the case of a two-month-old infant with persistent jaundice associated with acute cholestasis, severe cytolysis and coagulopathy. After ruling out the most common causes of neonatal cholestasis (such as biliary atresia and Alagille syndrome) and managing a transient CMV-DNA positivity, the atypical combination of cholestasis with low GT and low serum bile acids raised suspicion of an inborn error of bile acid synthesis. Urinary bile acid profiling (ESI-MS/MS) and whole genome sequencing confirmed the diagnosis, revealing a homozygous variant in the AKR1D1 gene, which causes congenital bile acid synthesis defect type 2 (BASD2). Prompt initiation of oral cholic acid replacement therapy led to complete resolution of jaundice, regression of cholestasis, normalisation of liver function tests and prevented progression to cirrhosis. The case underscores the crucial importance of considering rare bile acid synthesis defects in infants presenting with low GT cholestasis.