Children with infantile nephropathic cystinosis suffer from an autosomal recessive genetic defect that disrupts the lysosomal transport of cystine, producing cystine accumulation in many organs, including kidney, cornea, thyroid gland, and brain. Preliminary studies have identified a specific cognitive impairment in short-term visual memory for both cystinostics and obligate heterozygous carriers of the gene. We propose to perform extensive neurobehavioral, chemical and ophthalmologic studies on additional groups of cystinotic children, their heterozygous parents, and siblings who are potential carriers, as well as appropriate normal, renal disease, and hypothyroid control groups to confirm and specifically define the underlying mechanisms responsible for this cognitive deficit. Such a multidisciplinary approach has the potential to provide unique insights into brain/behavior relationships. This research could establish that certain neuronal populations, i.e. those responsible for the development of short-term visual memory functioning, are particularly susceptible to the accumulation of cystine. Such a discovery is a special relevance for heterozygotic carriers of other genetic disorders, who also may suffer from specific cognitive impairments that as yet are unidentified.
Showing the most recent 10 out of 15 publications
