Long-term follow-up of neurocognitive function in patients with citrin deficiency and cholestasis

Background: Citrin deficiency is a rare metabolic disor der prevalent in East and Southeast Asia that affects liver or neurological function throughout various life stages. While early diagnosis and dietary management can improve prognosis for infant onset disease, data on long term neurocognitive outcomes is scarce. Purpose: This study aimed to clarify whether transient metabolic disturbances during early childhood have a lasting effect on the neurocognitive function of indivi duals with citrin deficiency. Methods: Thirty patients diagnosed with citrin deficiency prior to 1 year of age underwent neuropsychological as sessments including attention deficit/hyperactivity disor ders (ADHD) and intelligence quotient (IQ). We compared the peak laboratory values during infancy between child ren who were versus were not later diagnosed with ADHD. Results: Neurocognitive assessments of 30 individuals with citrin deficiency aged 3-25 years revealed that full scale IQ scores were normally distributed. Of this cohort, 47% (14 of 30) were diagnosed with ADHD: 6, 6, and 2 with the combined, inattentive, and hyperactive impulsive types, respectively. This prevalence was higher than that in the general population (1.7%-16%). Moreover, a one unit increase in ammonia levels before 1 year of age was associated with a 1.023 fold increase in the likelihood of future hyperactivity impulsivity symptoms (P=0.038; 95%confidence interval, 1.001-1.046). Despite these find ings, this longterm followup of individuals with citrin deficiency indicated that it had minimal impact on neuro cognitive function, allowing for a generally normal life. Conclusion: Patients with a history of cholestasis caused by citrin deficiency during infancy have a greater inci dence of ADHD than the general population, suggesting that metabolic disturbances during early childhood in individuals with citrin deficiency may have a longterm negative impact on their neurocognitive function.