Nephropathic cystinosis with central nervous system involvement

Jonas, Adam J.; Conley, Susan B.; Marshall, R. B; Johnson, Rebecca A.; Marks, M. David; Rosenberg, Harvey S.

doi:10.1016/0002-9343(87)90661-9

Cited by 66 publications

(39 citation statements)

References 12 publications

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“…Nine of 80 patients had central nervous system abnormalities that ranged from speech difficulties to severe impairments of swallowing and walking (27). Cerebral atrophy has also been observed on computerized axial tomography (28,29). The progressive involvement of tissues other than the kidney emphasizes the need for continuous aggressive treatment.…”

Section: Smolin Et Almentioning

confidence: 99%

A Comparison of the Effectiveness of Cysteamine and Phosphocysteamine in Elevating Plasma Cysteamine Concentration and Decreasing Leukocyte Free Cystine in Nephropathic Cystinosis

et al. 1988

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ABSTRACT. Cysteamine (B-mercaptoethylamine, MEA) is currently used to treat children with nephropathic cystinosis. In this study MEA was compared to phosphocysteamine (MEAP), a phosphorothioester that tastes and smells better than MEA, with respect to its ability to elevate plasma MEA and deplete leukocytes of cystine. Studies were performed in six children with nephropathic cystinosis ranging in age from 2 to 10 yr. After equimolar oral doses of either MEA or MEAP plasma cysteamine was determined at various times for 6 h. MEA was determined by sodium borohydride reduction followed by highperformance liquid chromatography separation and el&-trochemical detection. Leukocyte cystine was measured before and 1 and 6 h after drug administration. Peak plasma MEA was obtained 30 min to 1 h after a dose and was not significantly different when MEA (48.6 f 10.7, mean + SD) or MEAP (54.1 f 20.2) was given. Significant plasma MEA concentrations were seen as early as 15 min after an oral dose, indicating rapid absorption. Analysis of vomitus indicated that hydrolysis of the phosphate group of MEAP occurs in the stomach. The percent decrease in leukocyte cystine content obtained with MEA administration (61.9%) was not significantly different from the decrease observed when MEAP was administered (65.3%). MEA and MEAP appear to be equally effective in their cystine-depleting properties. (Pediatr Res 23: 616-620, 1988) Abbreviations MEA, cysteamine MEAP, phosphocysteamine MEA (P-mercaptoethylamine) has been used since 1979 as a part of a national collaborative study to treat children with

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Section: Smolin Et Almentioning

confidence: 99%

A Comparison of the Effectiveness of Cysteamine and Phosphocysteamine in Elevating Plasma Cysteamine Concentration and Decreasing Leukocyte Free Cystine in Nephropathic Cystinosis

et al. 1988

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“…The organ affected most severely early in life is the kidney, but most other organs are affected as well [Gahl et al, 2001]. Neuroimaging and neuropathological studies of individuals with cystinosis have demonstrated central nervous system (CNS) involvement, including cerebral atrophy, white matter necrosis, patchy demyelination, and brain cystine accumulation [Ehrich et al, 1979;Levine and Paparo, 1982;Ross et al, 1982;Cochat et al, 1986;Gahl and Kaiser-Kupfer, 1987;Jonas et al, 1987;Fink et al, 1989;Nichols et al, 1990;Vogel et al, 1990].Studies examining cognitive functioning in individuals with cystinosis have shown overall intelligence within the normal range as well as average performance in the areas of language and auditory processing [Nichols et al, 1990]. In contrast, individuals with cystinosis perform more poorly than controls on tests of visual memory [Trauner et al, 1988] and visualmotor integration [Scarvie et al, 1996].…”

mentioning

confidence: 99%

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

Spilkin

Ballantyne

Babchuck

et al. 2007

American J of Med Genetics Pt B

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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.

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“…Although cystine accumulates most prominently in renal, hepatic, gastrointestinal mucosal, and reticuloendothelial cells, cystine deposition also occurs in the choroid plexus, meninges, and brain parenchyma. [17][18][19][20][21][22] Postmortem observations have led to the postulate that hydrocephalus results from abnormal secretion of CSF by an infiltrated choroid plexus. 17 A significant body of evidence supports decreased CSF absorption secondary to increased resistance to CSF flow through arachnoid villi, rather than increased CSF production by the choroid plexus, as the most likely mechanism responsible for IIH.…”

Section: Case Reportsmentioning

confidence: 99%