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Original Article

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

Meng-Ju Melody Tsai^1,2  , Jung-Chi Chang^3,4  , Heng-Yu Lu⁵, Susan Shur-Fen Gau^3,4  , Yin-Hsiu Chien⁶  , Wuh-Liang Hwu^6,7  , Yen-Hsuan Ni^1,8  , Huey-Ling Chen^8,9  , Ni-Chung Lee⁶ 

¹Department of Pediatrics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan
²Department of Pediatrics, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan
³Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
⁴Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
⁵Graduate Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
⁶Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan
⁷Center for Precision Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan
⁸Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
⁹Department of Medical Education and Bioethics, National Taiwan University College of Medicine, Taipei, Taiwan

Correspondence Ni-Chung Lee ,Tel: 886-2-23123456, Email: ncleentu@ntu.edu.tw

Received: July 28, 2024; Revised: September 22, 2024   Accepted: October 18, 2024.

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.

Keywords :Neuropsychological evaluation, Attention deficit hyperactivity disorder, Citrullinemia type II, Citrin deficiency