The status of adult patients with citrin deficiency in Japan: A report from the nation-wide study

Long-term outcomes in adult patients with citrin deficiency have remained poorly understood and often underrepresented in cohort studies, particularly in patients with adolescent and adult citrin deficiency (AACD). To address this gap, the present study analyzed clinical data from 128 Japanese adult citrin deficiency patients, the largest cohort and first study of its kind, providing important insights into the clinical course of citrin deficiency in adulthood.

Patients were grouped by disease onset into neonatal intrahepatic cholestasis caused by CD (NICCD), post-NICCD, and AACD. Adults with a history of NICCD generally showed favorable long-term outcomes, while those diagnosed later with AACD were more likely to develop persistent or worsening symptoms, including hepatic encephalopathy, intellectual disability, and reduced quality of life. The hepatic condition observed in AACD was hypothesized to resemble end-stage metabolic dysfunction-associated steatotic liver disease (MASLD), suggesting that patients may experience irreversible liver damage. These findings underscore the importance of early diagnosis and sustained intervention to improve long-term prognosis.