Non‐verbal deficits in young children with a genetic metabolic disorder: WPPSI‐III performance in cystinosis

Abstract

Cystinosis is a recessive genetic metabolic disorder in which the amino acid cystine accumulates in various organs of the body. Previous studies have demonstrated visuospatial dysfunction in children and adults with this disorder. It is not known whether this is a result of the genetic alteration or an accumulation of cystine in the brain over time. This study investigated patterns of performance in 20 young children with cystinosis (4-7 years) and 20 matched controls on the Wechsler Preschool and Primary Scale of Intelligence-Third Edition (WPPSI-III). The children with cystinosis had a mean Full Scale IQ at the low end of the average range. Their overall cognitive functioning was comprised of average verbal abilities, low average non-verbal abilities, and low average processing speed. Multivariate analyses indicated that the cystinosis and control groups were not significantly different on the verbal subtests. In contrast, the cystinosis group performed significantly more poorly than controls on the performance and processing speed subtests. Although overall intellectual function was in the normal range, young children with cystinosis demonstrated a discrepancy such that non-verbal abilities were poorer relative to verbal abilities. This pattern resembles the cognitive profile found previously in older individuals with cystinosis and indicates that the specific cognitive profile emerges early in development. These findings suggest that the cognitive dysfunction in cystinosis is not merely the result of cystine accumulation over time but may be related to differences in brain development as a consequence of alterations or deletions of the cystinosin gene.

Differential gene expression in patients with subsyndromal symptomatic depression and major depressive disorder

“…Some study show it is a homophilic receptor expressed on T cells, B cells, dendritic cells, monocytes, macrophages,eosinophils, mast cells, granulocytes, and platelets[14]. CD84 expression increases the following activation of T cells, B cellsand dendritic cells[15]. CD84 is also a hemophilic family member that enhances IFN-_ secretion in activated T cells.…”

Nephropathic cystinosis: late complications of a multisystemic disease

“…Children with cystinosis have mean full scale IQs in the low normal range [99][100][101], with impaired tactile recognition of common objects and difficulty processing visual information [102,103]. Even children with normal composite IQs have low visual memory subtest scores, and their academic performance is usually lower than normal.…”

“…Nichols et al showed an association between the degree of cortical atrophy and the severity of impairment in visual short-term memory performance [104]. Others reported that children with cystinosis are at greater than normal risk for developing behavioral difficulties and social problems [99,105]. Besides cystinosis, renal failure, long-standing dialysis, and growth retardation themselves can lead to difficulties in psychosocial adjustment requiring psychotherapy.…”

Neurological impairment in nephropathic cystinosis: motor coordination deficits

“…Neuropsychological studies have shown that individuals with cystinosis have IQ and language within the normal range [13, 14] but specific nonverbal deficits [15, 16]. In particular, deficits are seen in the domains of visual spatial skills, visual–motor integration, visual memory, and processing speed, with a sparing of visual perception [15–19].…”

“…In particular, deficits are seen in the domains of visual spatial skills, visual–motor integration, visual memory, and processing speed, with a sparing of visual perception [15–19]. This specific pattern has been observed across the age range from preschool through adulthood [15, 16, 18], suggesting the possibility that the genetic disorder may exert a very early effect on brain development rather than the neurological effects being the result of a progressive decline in cognitive functioning as cystine continues to accumulate in the brain.…”