Swallowing Dysfunction in Nephropathic Cystinosis

Sonies, Barbara C.; Ekman, Evan F.; Andersson, Hans; Adamson, Megan; Kaler, Stephen G.; Markello, Thomas C.; Gahl, William A.

doi:10.1056/nejm199008303230903

Cited by 71 publications

(45 citation statements)

References 18 publications

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“…In untreated cystinosis, the inexorable progression of renal glomerular dysfunction leads to uremia and death by 9-10 y of age, unless dialysis or renal transplantation intervenes (6,7). Cystinosis also results in growth retardation, hypothyroidism, photophobia, retinal damage, posterior synechiae and corneal ulcerations (8), pancreatic exocrine and endocrine insufficiency (9, lo), a distal vacuolar myopathy (11,12), swallowing difficulties (13), and CNS involvement (14). These complications occur with variable frequencies and severities, and at different times in life.…”

mentioning

confidence: 99%

Intravenous Cysteamine Therapy for Nephropathic Cystinosis

et al. 1995

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confidence: 99%

Intravenous Cysteamine Therapy for Nephropathic Cystinosis

et al. 1995

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“…Infants with cystinosis are normal at birth but develop renal tubular Fanconi syndrome at 6 to 12 mo of age and renal failure at approximately 10 yr of age (8). In addition, hypothyroidism (1,2), myopathy (9,10), swallowing dysfunction (11), diabetes (12), male hypogonadism (13), pulmonary dysfunction (14), and central nervous system involvement (15)(16)(17) complicate this disorder in adolescence and early adulthood (18).…”

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confidence: 99%

Coronary Artery and Other Vascular Calcifications in Patients with Cystinosis after Kidney Transplantation

Ueda¹,

O’Brien²,

Rosing³

et al. 2006

Clinical Journal of the American Society of Nephrology

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Cystinosis, an autosomal recessive disorder of lysosomal cystine accumulation, results from mutations in the CTNS gene that encodes the lysosomal cystine transporter, cystinosin. Renal tubular Fanconi syndrome occurs in infancy, followed by rickets, growth retardation, photophobia, and renal failure, which requires renal transplantation at approximately 10 yr of age. Treatment with cysteamine decreases cellular cystine levels, retards renal deterioration, and allows for normal growth. Patients with a history of inadequate cystine depletion therapy may survive, after renal transplantation, into the third to fifth decades but will experience other, extrarenal complications of the disease. Routine chest and head computed tomography scans of 41 posttransplantation patients with cystinosis were reviewed for vascular calcification. The radiologic procedures had been performed to examine lung and brain parenchyma, so there was little ascertainment bias. Thirteen of the 41 patients had vascular calcification, including 11 with coronary artery calcification. One 25-yr-old man required three-vessel coronary artery bypass graft surgery. There were no significant differences between the 13 patients with calcification and the 28 without calcification in the following parameters: Time on dialysis, frequency of transplantation, hypertension, hypercholesterolemia, homozygosity for the 57-kb deletion in CTNS, serum creatinine, and calcium-phosphate product. However, the finding of vascular calcification correlated directly with duration of life without cysteamine therapy and inversely with duration of life under good cystine-depleting therapy. The accumulation of intracellular cystine itself maybe a risk factor for vascular calcifications, and older patients with cystinosis should be screened for this complication.

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“…The classic disorder is characterized clinically by renal tubular Fanconi syndrome in the first year of life, growth retardation in childhood, renal glomerular failure at ∼10 years of age, hypothyroidism, and a variety of other complications, including photophobia and corneal crystal formation (Gahl 1986;Gahl et al 1995). After renal transplantation, cystine accumulation continues in nonrenal organs, frequently causing a distal vacuolar myopathy (Charnas et al 1994), swallowing difficulty (Sonies et al 1990), or retinal dysfunction (Kaiser-Kupfer et al 1986), and occasionally causing diabetes mellitus (Fivush et al 1987), pancreatic exocrine insufficiency (Fivush et al 1988), or neurological deterioration (Ehrich et al 1979;Fink et al 1989). These complications arise because defective lysosomal transport of the disulfide cystine (Gahl et al 1982a) causes this amino acid to accumulate within the lyso-somes of many different cell types, which then triggers cystine crystal formation (Gahl et al 1982b).…”

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The Genomic Region Encompassing the Nephropathic Cystinosis Gene (CTNS): Complete Sequencing of a 200-kb Segment and Discovery of a Novel Gene within the Common Cystinosis-Causing Deletion

et al. 2000

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Nephropathic cystinosis is an autosomal recessive disorder caused by the defective transport of cystine out of lysosomes. Recently, the causative gene (CTNS) was identified and presumed to encode an integral membrane protein called cystinosin. Many of the disease-associated mutations in CTNS are deletions, including one >55 kb in size that represents the most common cystinosis allele encountered to date. In an effort to determine the precise genomic organization of CTNS and to gain sequence-based insight about the DNA within and flanking cystinosis-associated deletions, we mapped and sequenced the region of human chromosome 17p13 encompassing CTNS. Specifically, a bacterial artificial chromosome (BAC)-based physical map spanning CTNS was constructed by sequence-tagged site (STS)-content mapping. The resulting BAC contig provided the relative order of 43 STSs. Two overlapping BACs, which together contain all of the CTNS exons as well as extensive amounts of flanking DNA, were selected and subjected to shotgun sequencing. A total of 200,237 bp of contiguous, high-accuracy sequence was generated. Analysis of the resulting data revealed a number of interesting features about this genomic region, including the long-range organization of CTNS, insight about the breakpoints and intervening DNA associated with the common cystinosis-causing deletion, and structural information about five genes neighboring CTNS (human ortholog of rat vanilloid receptor subtype 1 gene, CARKL, P2X5, and HUMINAE). In particular, sequence analysis detected the presence of a novel gene (CARKL) residing within the most common cystinosis-causing deletion. This gene encodes a previously unknown protein that is predicted to function as a carbohydrate kinase. Interestingly, both CTNS and CARKL are absent in nearly half of all cystinosis patients (i.e., those homozygous for the common deletion).

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Swallowing Dysfunction in Nephropathic Cystinosis

Cited by 71 publications

References 18 publications

Intravenous Cysteamine Therapy for Nephropathic Cystinosis

Intravenous Cysteamine Therapy for Nephropathic Cystinosis

Coronary Artery and Other Vascular Calcifications in Patients with Cystinosis after Kidney Transplantation

The Genomic Region Encompassing the Nephropathic Cystinosis Gene (CTNS): Complete Sequencing of a 200-kb Segment and Discovery of a Novel Gene within the Common Cystinosis-Causing Deletion

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