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

Abstract

Background: Citrin deficiency is a rare metabolic disorder 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 individuals with citrin deficiency.

Methods: Thirty patients diagnosed with citrin deficiency prior to 1 year of age underwent neuropsychological assessments including attention-deficit/hyperactivity disorder (ADHD) and intelligence quotient (IQ). We compared the peak laboratory values during infancy between children 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: six, six, and two 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 findings, this long-term follow-up of individuals with citrin deficiency indicated that it had minimal impact on neurocognitive function, allowing for a generally normal life.

Conclusion: Patients with a history of cholestasis caused by citrin deficiency during infancy have a greater incidence of ADHD than the general population, suggesting that metabolic disturbances during early childhood in individuals with citrin deficiency may have a long-term negative impact on their neurocognitive function.