Integrated genomic and biochemical diagnosis of a novel homozygous start-loss variant in AKR1D1 associated with neonatal cholestasis.
Alberto Izquierdo-Martínez, Jose Luis Rubio-Prieto, Ana Rodriguez-Rodriguez et al.
✦ AI-curated · Sources linked
Case in brief
A 3-month-old male presented with severe neonatal cholestasis and elevated tyrosine levels detected in newborn screening. Despite transient normalization of tyrosine, recurrent hyper-tyrosinemia and progressive cholestasis ensued, leading to coagulopathy and hyperbilirubinemia. Imaging showed no liver abnormalities. Genetic testing revealed a novel homozygous start-loss variant in AKR1D1, confirming bile acid synthesis defect type 2. Treatment with oral cholic acid resulted in clinical and biochemical improvement.
Diagnostic / clinical pearl
This case underscores the diagnostic challenges of neonatal cholestasis, emphasizing the need for comprehensive metabolic evaluation and genetic testing when initial findings are inconclusive.
Why it matters
The case highlights the significance of early molecular diagnosis in managing congenital bile acid synthesis defects, which can prevent severe complications and improve patient outcomes.