The prognosis of citrin deficiency differs between early-identified newborn and later-onset symptomatic infants.

backgroundThe prognosis for patients with citrin deficiency is not always benign. This study examined the differences between patients identified early by newborn screening and patients identified later with cholestasis/hepatitis. MATERIALS AND

methodsThis retrospective study included 42 patients with genetically confirmed SLC25A13 mutations who were born between May 1996 and August 2019. Fifteen patients were identified during newborn screening (NBS group) and 27 patients were identified through the onset of cholestasis/hepatitis in infancy (clinical group).

resultsOverall, 90% of the patients presented with cholestasis, among whom 86% (31/36) recovered at a median age of 174 days. Compared with patients in the clinical group, patients in the NBS group were significantly younger at diagnosis and at cholestasis-free achievement; they also had significantly lower levels of peak direct bilirubin and liver enzymes. At the median follow-up age of 11.8 years, 21% of the patients had dyslipidemia, whereas 36% of the patients had failure to thrive. The overall mortality rate was 2.4%. Variant c.851_854del was the most frequent, constituting 44% of the mutant alleles.

conclusionPatients identified early by NBS had a better prognosis, demonstrating the importance of a timely diagnosis of NICCD and the need for careful follow-up. IMPACT: Some cases of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) are not benign. Compared with patients identified later based on the presence of cholestasis/hepatitis, patients identified early by newborn screening have less severe cholestasis and are cholestasis-free at a significantly younger age. A timely diagnosis is needed, along with follow-up examinations that assess metabolic profile and body weight, to improve the long-term prognosis of NICCD patients.