Table 4 Review of the literature on neurocognitive data in cystinosis patients. (VMI: Visual Motor Integration). Regarding the neuropsychological studies, 11/15 (73.3%) included a control group.

Jonas, 1987 [22]

WAIS-III

1

89

NA

NA

90

NA

This patient never attended school, but she received home-bound teaching and obtained a high school diploma.

Trauner, 1988 [20]

unaffected sibling control group (n = 12); chronic renal failure contrôle group (n = 8)

18/22 (selection of 5 subtests)

No difference from their siblings on composite IQ; significantly higher than the scores from patients with renal failure; bead memory subtest significantly below the norm in cystinosis patietns (p < 0,001): deficit in short term visual memory

Nichols, 1990 [9]

no

8/11 (abbreviated version)

Benton Visual Retention test (n = 11); Beery test of visual motor integration (n = 11)

Children with the greatest degree of atrophy had the poorest performance on all cognitive tests, however only the relationship beween atrophy and short-term memory approached significance (p = 0.06); short-term memory was assessed with 2 subtest: bead memory (visual) and memory for sentences (auditory): poorer performance on visual memory

Ballantyne, 1997 [16]

age-, sex- and IQ matched healthy control group (n = 19)

19

Wide Range Achievement Test-Revised (n = 19)

All patients had IQ within the normal range; performed significantly more poorly on arithmetic sub-score compared to controls (p = 0,001), trends on spelling (p = 0,085); no deterioration of function with age; all but 2 were grade-appropriate for their age (one was a year behind, the other one year advanced)

Ballantyne, 2000 [34]

healthy control group (n = 108)

33

Visuospatial test^a; visuoperceptual tests^b; visual scanning tests^c

Mean IQ within the normal range; All comparisons on the other tests were based on raw scores and revealed: impairment in spatial processing (extrapersonal orientation, mental rotation, short-term memory of spatial location) whereas perceptual processing was largely intact

Delgado, 2005 [42]

healthy control group (n = 101) and cystic fibrosis patients (n = 21)

Achenbach Child Behavior CheckList (n = 64): Total score, Internalizing and Externalizing behavior

The group means for all scales were within the normal range, but rates of clinically significant scores were higher on the total problems summary scale and the internalizing problems summary scale; significant differences compared to controls on: social problems (immature behavior), somatic complaints, attention problems, and aggressive behaviors

Trauner, 2007 [35]

age-matched control group (n = 25)

WPPSI-III, WISC-III, WISC-IV

25

NA

NA

12.73

NA

NA

Gollin Incomplete Figures (n = 25), Motor-Free Visual Perception Test (n = 25), Beery-Buktenica Developmental Test of VMI 5th ed. (n = 25) including visual perception supplemental test; K-ABC spatial memory sub-test (n = 25), Spatial Relations Test of the Woodcock-Johnson Psycho-educational battery 3rd ed. (n = 25)

TIQ and PIQ were not reported; significant lower VIQ in NC patients compared to controls (although VIQ was within the normal range in NC patients); a significant impairment in visual spatial and visual motor skills was found in young children with NC, whereas no significant difference on visual perceptual tests.

Spilkin, 2007 [18]

20 age-matched typically developped controls

WPPSI-III

20

90.85

10.8

10.7

89

12.9

Mean TIQ at the low end of the average range, average verbal abilities, low average non-verbal abilities and processing speed, discrepancy between verbal and non-verbal abilities

Ulmer, 2009 [33]

no

WISC-III

7

92

[71-105]

[76-118]

90

[68-97]

Zurich Neuromotor assessment (n = 8); Child Behavior Checklist (n = 8); the TNO-AZL quality of life questionnaire (child- and parent-forms, n = 7); K-ABC (n = 2, included in the mean of IQ reported using WISC-III)

Total IQ was significantly lower in NC patients compared to controls. Verbal IQ was significantly higher than performance (p = 0,03). Motor performance was significantly below the norm. The patients’ QOL was normal for six of seven dimensions, whereas parents’ QOL rated only 3 of seven dimensions as normal. Psychosocial ajustment was signficantly impaired in NC patients.

Trauner, 2010 [21]

49 controls [2-17] years

WPPSI-III or WISC-III or WAIS-III, WISC-IV

52

+/−12,5

89.27

+/− 14,7

motor coordination supplemental test of Beery test of visual motor integration (n = 52)

In the younger group (preacademic): no significant differences between NC patients and controls on VIQ, but significantly lower PIQ; in the older group (school age): both VIQ and PIQ were significantly lower in NC patients; persistant non progressive, fine-motor coordination deficit in NC patients

Bava, 2010 [32]

24 TD age-matched controls

WISC-R or WISC III

24

+/−12,2

90

+/−12

Beery test of VMI (n = 24); Spatial Relations Test of the Woodcock-Johnson Psycho-educational battery third edition (n = 24)

NC patients had lower scores than controls on both visuospatial functionning measures and on both measures of intellectual functioning (PIQ and VIQ)

Besouw, 2010 [37]

no

WISC-III (n = 13) and WAIS-III (n = 1)

14

87

[60-132]

[60-125]

87

[65-130]

Beery test of visual motor integration (n = 14); Stroop Color-Word Interference Test (n = 11); Bourdon-Vos test (n = 13); Rey-Osterrieth complex figure (n = 12); computerized drawing task (n = 14); Child BehaviorChecklist (n = 14)

Median Total IQ was below the average of normal population in NC patients with a discrepancy between verbal and performance IQ; 50% of NC patients scored poorly on visual-motor integration (VMI < 85), 69% had sustained attention impairment, none had a good visual memory score, only one had good planning skills and two (14%) had a good score on processing speed. No significant difference was noted on behavioural and emotional functioning.

Ballantyne, 2013 [17]

24 age-matched healthy controls (mean age:12,1 years, [8,1-17,8]

Stroop Color-Word Interference Test (n = 28); Delis-Kaplan executive function system (D-KEFS, n = 28); Behavior Rating Inventory of Excecutive Function (BRIEF questionnaire, n = 28)

Higher incidence of executive dysfunction in NC patients (including attention, initiation, motor speed, fluency, simultaneous processing, speed of processing, cognitive flexibility, inhibiting prepotent responses, abstract thought)

Viltz, 2013 [36]

age-matched control group (n = 85)

WISC-III

46 (with 2 groups: early n = 32 / late treatment n = 14)

88.5

early ttt: 94(+/−12,5)/late ttt: 83(+/−  15,1)

early ttt: 98,2(+/−11,1)/late ttt: 88,6(+/−15,2)

87.2

early ttt: 92,7(+/−15,3)/late ttt: 81,6(+/−13,2)

Beery test of VMI (n = 41); Spatial Relations Test of the Woodcock-Johnson Psycho-educational battery third edition (n = 40)

NC patients scored significantly lower on visuomotor skills compared with controls; NC patients scored lower on IQ measures and visuo-spatial skills when treated at or after age 2 years compared with NC patients treated before the age of 2 years and controls.

Aly, 2014 [31]

13 age- and sex-matched healthy controls

13 (arabic version, second edition)

Child Behavior Checklist (n = 13); Porteus Maze Test (Visuospatial ability and visuomotor coordination, n = 13)

Total IQ was significantly lower in NC patients compared to controls; both verbal and non verbal and non verbal abilities being impaired; the non verbal abilities were lower (but did not reach statistical significance); visuospatial abilities were significantly lower compared to visual perception; NC patients had more behavioral problems compared to healthy controls; NC patients had lower socioeconomic status in this study.