Infantile nephropathic cystinosis is an autosomal recessive disorder of cystine transport which results in cystine accumulation in many organs, including kidneys, cornea, thyroid and brain. Heterozygous carriers of the gene for cystinosis have lower levels of cystine accumulation than homozygotes, (but higher levels than noncarriers), and are asymptomatic from a medical standpoint. Previous work has documented a specific cognitive deficit in visual spatial function in children with cystinosis. A similar cognitive profile is present in adult heterozygous carriers for the gene, but appears to require longer to develop than in the homozygotes. The present proposal is a longitudinal study with several goals. The first is to define more precisely the step in visual processing that is impaired in children with cystinosis, focusing on mental imagery and mental rotation of objects. Children will be tested longitudinally to determine whether severity of the cognitive deficit increases over time, or whether their medical treatment prevents worsening of the problem. The second goal is to study the characteristics and progression of the cognitive deficit over time in heterozygotes. The third is to use quantitative magnetic resonance imaging morphometric techniques to measure specific cortical and subcortical brain areas in subjects with cystinosis and in heterozygous adults. This approach provide a unique opportunity to study brain-behavior relationships in children with a specific genetic disorder, as well as in heterozygous carriers. Information gained may increase understanding of neuro-anatomic correlates of visual processing in humans. The study has potential implications for future treatment of heterozygous carriers, if the cognitive deficit is impairing functional ability. Finally, this work has special relevance for heterozygous carriers of other genetic disorders, who also may suffer from specific cognitive impairments that are as yet unrecognized.
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