Neonatal Acute Liver Failure due to Citrin Deficiency (NALFCD)

Area of Science:

• Biochemistry
• Genetics
• Pediatrics

Background:

• Citrin deficiency (CD) and citrullinemia type I (CTLN1) are metabolic disorders often detected by elevated citrulline in newborn screening (NBS).
• These conditions require different management strategies, posing therapeutic challenges during the diagnostic period.
• Neonatal acute liver failure can be a presentation for both CD and CTLN1.

Purpose of the Study:

• To report a case of citrin deficiency presenting as neonatal acute liver failure without cholestasis.
• To highlight the importance of differentiating CD from CTLN1 in infants with elevated citrulline on NBS.
• To emphasize the need for safe and effective interim treatment strategies while awaiting diagnostic confirmation.

Main Methods:

• A case report of a Chinese infant with elevated citrulline on NBS.
• Clinical presentation, laboratory investigations (INR, albumin, ammonia, bilirubin, liver enzymes), and response to initial treatment were analyzed.
• Genetic analysis of the SLC25A13 gene was performed for definitive diagnosis.

Main Results:

• The patient presented with neonatal acute liver failure, elevated citrulline, and coagulopathy.
• Initial management for suspected CTLN1 (protein restriction, high glucose) worsened liver function.
• Switching to a lactose-free, MCT-enriched formula led to rapid clinical improvement, confirming CD.
• Genetic analysis revealed compound heterozygous pathogenic mutations in SLC25A13.

Conclusions:

• This case represents the first report of citrin deficiency presenting with neonatal acute liver failure without cholestasis.
• Accurate and timely differentiation between CD and CTLN1 is critical for appropriate management and improved outcomes.
• Effective interim treatment strategies are essential for infants identified through NBS recalls for inborn errors of metabolism.