In this study, we compared children with NCTN to age- and sex-matched children with CKD, to observe any significant differences in neurocognitive functions and behavioural profiles as most of previous studies compared them with healthy control to figure out if cystinosis apart from renal dysfunction can affect these functions.
In our study, there was no significant difference in the overall intelligence quotient between NCTN children and patients with CKD. Both groups had low total IQ score (below 90); however, higher percentage of children with NCTN (50%) compared to CKD group (33%) had mild mental retardation or slow learning, and this comes with conclusion made by Trauner and his colleagues who suggested that neurocognitive dysfunction cannot be attributed only to renal impairment .
In NCTN group, children with CKD stage 1 had median IQ score 94.5 tested by SB test that was higher than children with more advanced stages, but it was not statistically significant (p-value = 0.68). This may be due to the small number of patients with NCTN in each CKD stage, and this was consistent with the study that found IQ is positively correlated with eGFR  and another cohort study of 855 adults with CKD which concluded that lower eGFR was associated with lower scores in most cognitive domains .
We found that there was no significant difference between both groups regarding emotional and behavioural problems tested by CBCL (total score 75.45 ± 7.8 and 76.77 ± 9.4, respectively with p = 0.608); this is contrary to an earlier study done in the same setting that reported a significant difference in emotional and behavioural problems in NCTN children compared to control (total score NCTN children 62.9 ± 7.9, control 48.1 ± 5.5 with p = 0.004) . However, they compared NCTN children with healthy children not CKD children unlike our study. Additionally, all of our patients with NCTN were on cysteamine treatment for more than 1 year.
In our study, it was observed that the mean total score for behavioural and emotional problems was significantly high in NCTN children (75.45 ± 7.8). This supports a previous study reporting that children with cystinosis were at a higher risk for behavioural problems . Delgado and colleagues compared NCTN children with healthy controls and cystic fibrosis children as they expected that chronic disease may have effects on behavioural and social functions; however, in our study, we demonstrated higher mean T score on CBCL (75.45 ± 7.8), especially regarding somatic complaints, withdrawn behaviour, and anxious/depressed behaviour . This might be explained by low socioeconomic status, low schooling rate, and lack of psychosocial support observed in our cases.
In our study, we found a negative correlation between duration of cysteamine therapy and some items tested by SB test and CBCL (short-term memory, thought, and sexual problems). By increasing duration of cysteamine therapy, there was significant improvement in some behavioural functions (thought problems, sex problems). This is presumably due to the positive effect of treatment on thyroid and renal functions that can have an impact on behavioural functions . Additionally, cysteamine prevents late complications of cystinosis, which includes neurological symptoms .
There was deterioration of some neurocognitive functions (short-term memory) by increasing the duration of cysteamine treatment, as observed in our study. This may be due to late initiation and lack of persistent treatment, as long-term studies have shown that when cysteamine was given early, it prevented neurocognitive dysfunctions [10,11,12].
Despite being on cysteamine treatment for 12 months or more, children with NCTN had poor performance on SB scale (score less than 90), so neurocognitive deficits cannot be explained by cysteine accumulation or even renal dysfunction (CKD group had better score for visual reasoning); this could raise the possibility of CTNS gene impact on brain function as evidenced by asymptomatic carriers of the gene, who have normal kidney functions and no cysteine accumulation, and demonstrated cognitive deficits similar to homozygous individuals with cystinosis .
This was an analytical cohort study, we were unable to assess changes in neurocognitive function over time. Moreover, the small sample size in children with NCTN and CKD limited our ability to detect effects of variables such as eGFR, gender, and age on neurocognitive functions and behavioural profiles. Additionally, we did not take in consideration the social status and educational level of the parents that could have a large impact on their children’s behavioural profiles. We did not employ a baseline psychometric assessment before the start of cysteamine therapy or objective monitoring of treatment compliance due to unavailability of WBC cysteine essay.
We suggest to perform this study on a large scale of children with NCTN with normal renal function, follow-up of these patients over a long duration of time, and to correlate this psychometric assessment to the onset of treatment, WBC cysteine assay, and type of genetic mutation.