February 21, 1997

Although our NIH grant has not as yet been re-funded, we are continuing to conduct research on the neuro-behavioral consequences of cystinosis and the cystinosis gene, thanks to the generosity of the National Cystinosis Foundation. We have re-submitted the NIH grant proposal, and are awaiting news from the reviewers. We do plan to test families at the annual meeting to be held in San Diego in July. We would like to update you on some of our recent research progress.

Angela received her doctoral degree in June of 1996. Her doctoral dissertation was "Neuropsychological correlates of a genetic metabolic disorder: Further characterization of visual processing deficits in infantile nephropathic cystinosis." In her dissertation, Dr. Ballantyne analyzed a great deal of data that we have been collecting from children with cystinosis over the past several years. Her main findings were that children with cystinosis demonstrate problems with the processing of visual-spatial information, whereas the processing ofvisual-perceptual information is intact. That is, there is a dissociation in visual processing in children with cystinosis. When asked to perform tasks involving visual-spatial skills, they may have more difficulty than most people. However, when asked to perform a task in which they have to analyze visual information that does not have a spatial component (for example, identifying objects from fragments of information, or recognition of faces), children with cystinosis are not likely to have problems. These results are important for several reasons. First, they suggest that certain areas of the brain may be more affected by cystinosis, while other areas are spared. Second, the results may have implications for learning styles in children with cystinosis; that is, they may learn more effectively by a combination of educational techniques which emphasize verbal and visual cues together, and by learning verbal mediation strategies to help them with spatial tasks. Academic areas which rely heavily on spatial cues (such as arithmetic) may present particular challenges to some children with cystinosis. In fact, in another paper which was recently accepted for publication in the American Journal of Medical Genetics: Neuropsychiatric Genetics, we looked at academic performance in children and young adults with cystinosis and found that, as a group, their achievement in arithmetic was lower than average, while their achievement in reading was within the average range. This finding is consistent with what was mentioned above; i.e., some arithmetic functions rely heavily on spatial cues, and we would expect people with cystinosis to have more difficulty with those areas.

In another study, which was presented at the Child Neurology Society meeting in October, 1996, we analyzed results of a behavioral questionnaire that many parents completed for us. We had questionnaires from 33 children with cystinosis, 56 "controls," and 9 from another group of children with chronic medical problems, cystic fibrosis. We found that children with cystinosis were more likely to demonstrate social and attentional problems than were controls or children with cystic fibrosis. We believe that these behavioral differences may be related to the effects of cystinosis on the nervous system, rather than merely to a reaction to a chronic illness, since children with cystic fibrosis did not have similar problems. Further studies are needed to identify which children are more likely to have behavior problems (for example, are behavior problems related to their cognitive difficulties, or to the severity of their medical problems, or to some other factors?), and what effect different forms of treatment may have on these behaviors.

We are very excited about the information we are obtaining from our studies, and would like to pursue many more questions in the future. We have already collected a large amount of data which we are continuing to analyze. We would like to collect more data on specific questions in the future. For example, one very important question is the effect of cystinosis on the nervous system over time. We would very much like to obtain enough longitudinal data to be able to answer this question. We hope to obtain some of this information at the meeting in July. Future efforts in this area will depend on the availability of adequate research funding. The funding we are receiving through the Cystinosis Foundation is allowing us to continue to analyze the data we have already collected. We want to thank the Cystinosis Foundation for their ongoing support of our research endeavors, and we look forward to continuing to work with the families affected by cystinosis.

   -  Doris A. Trauner M.D. and Angela Ballantyne Ph.D.