Congenital Bile Acid Synthesis Defect Type 2 Mimicking Biliary Atresia: A Case Report of Delta-4-3-Oxosteroid 5-Beta-Reductase Deficiency in a Two-Month-Old Infant.

Neonatal cholestasis presents a complex diagnostic challenge, frequently necessitating the differentiation of numerous etiologies, including the anatomically correctable biliary atresia (BA), from various metabolic and genetic disorders. The timely and accurate identification of inborn errors of bile acid metabolism is particularly critical, as these conditions can lead to progressive liver damage if left untreated. Congenital bile acid synthesis defects (CBASDs) are rare autosomal recessive inborn errors of metabolism that can manifest as neonatal cholestasis. Their clinical and biochemical profile, particularly in cases of normal or low gamma-glutamyl transferase (GGT) in the setting of significant cholestasis, can mimic other causes of neonatal liver disease, most notably BA, thereby posing a significant diagnostic challenge. We report a two-month-old male infant presenting with early-onset cholestatic jaundice since day 20 of life. Clinical and ultrasonographic findings initially raised strong suspicion for BA. However, the biochemical profile of markedly elevated transaminases, cholestasis with normal-to-low GGT, massive hyperferritinemia, and relatively low total bile acids suggested a metabolic etiology. Urine bile acid profiling by liquid chromatography-tandem mass spectrometry revealed trace levels of primary bile acids with accumulation of Δ4-3-oxo intermediates. Next-generation sequencing has confirmed the diagnosis of CBASD type 2. Liver biopsy demonstrated giant cell hepatitis without ductal proliferation, thus definitively excluding BA and precluding the need for a Kasai portoenterostomy.