Nephropathic cystinosis: posterior segment manifestations and effects of cysteamine therapy.
ABSTRACT Cystinosis is a rare autosomal recessive lysosomal storage disorder characterized by the intracellular accumulation of cystine. Treatment involves intracellular cystine depletion with oral cysteamine. A wide spectrum of ocular pathologic features has been associated with nephropathic cystinosis. We used the largest documented cohort of patients in the world to study the posterior segment manifestations associated with infantile nephropathic cystinosis and to determine retrospectively the effect of chronic oral cysteamine therapy on the frequency of these abnormalities.
Cross-sectional study of a series of patients.
Two hundred eight patients with infantile nephropathic cystinosis were studied at the National Institutes of Health between 1976 and 2004.
All patients underwent an ophthalmic evaluation. Patients older than 11 years also underwent Humphrey static perimetry, and electrophysiological testing was performed when possible.
Visual acuity, retina findings, visual fields, and electroretinographic (ERG) findings.
Pigmentary changes with retinal pigment epithelial mottling, seen as early as infancy, were the most common posterior segment manifestations. Moderate to severe constriction of the visual fields, as well as moderate to severe reduction of rod- and cone-mediated ERG responses, was seen in older patients. The frequency of retinopathy correlated directly with time not receiving oral cysteamine therapy and inversely with time receiving oral cysteamine therapy.
Infantile nephropathic cystinosis has posterior segment complications that can contribute to significant visual handicap. Early initiation of oral cysteamine therapy can reduce the frequency of posterior segment complications in cystinosis patients.
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ABSTRACT: Cystinosis is a rare autosomal recessive metabolic disorder characterized by the intracellular accumulation of cystine, the disulfide of the amino acid cysteine, in many organs and tissues. Infantile nephropathic cystinosis is the most severe phenotype. Corneal crystal accumulation and pigmentary retinopathy were originally the most commonly described ophthalmic manifestations, but successful kidney transplantation significantly changed the natural history of the disease. As cystinosis patients now live longer, long-term complications in extrarenal tissues, including the eye, have become apparent. A case of an adult patient with infantile nephropathic cystinosis is reported. He presented with many long-term ocular complications of cystinosis. After 4 years of follow-up, the patient died from sepsis. Pathology of the phthisical eyes demonstrated numerous electron-transparent polygonal spaces, bounded by single membrane, in corneal cells, retinal pigment epithelial cells, and even choroidal endothelial cells. The ophthalmic manifestations and pathology of infantile nephropathic cystinosis are discussed and reviewed in light of the current report and other cases in the literature.Survey of Ophthalmology 01/2007; 52(1):97-105. DOI:10.1016/j.survophthal.2006.10.006 · 3.51 Impact Factor
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ABSTRACT: The full burden of nephropathic cystinosis in adulthood and the effects of long-term oral cysteamine therapy on its nonrenal complications have not been elucidated. To assess the severity of cystinosis in adults receiving and not receiving oral cysteamine therapy. Case series. National Institutes of Health Clinical Center. 100 persons (58 men and 42 women) age 18 to 45 years with nephropathic cystinosis examined between January 1985 and May 2006. Historical data were collected on renal transplantation, administration of oral cysteamine, and time and cause of death. Patients were evaluated for height and weight; thyroid, pulmonary, and swallowing function; muscle atrophy; hypogonadism (in men); retinopathy; vascular and cerebral calcifications; diabetes mellitus; and homozygosity for the common 57-kb deletion in CTNS. Laboratory studies were also performed. Of 100 adults with nephropathic cystinosis, 92 had received a renal allograft and 33 had died. At least half of the patients had hypothyroidism, hypergonadotropic hypogonadism (in men), pulmonary insufficiency, swallowing abnormalities, or myopathy. One third of the patients had retinopathy or vascular calcifications, and 24% had diabetes. Homozygosity for the 57-kb CTNS deletion was associated with an increased risk for death and morbidity. The 39 patients who received long-term (> or =8 years) oral cysteamine therapy were taller and heavier, had a renal allograft later in life, had lower cholesterol levels, and experienced fewer complications and deaths than patients who received cysteamine for fewer than 8 years. The frequency of diabetes mellitus, myopathy, pulmonary dysfunction, hypothyroidism, and death increased as time off cysteamine treatment increased, and it decreased as time on cysteamine therapy increased. The study was retrospective and not randomized. The criteria used to measure adequacy of treatment were arbitrary. Untreated nephropathic cystinosis causes extensive morbidity and death in adulthood. Long-term oral cysteamine therapy mitigates these effects.Annals of internal medicine 09/2007; 147(4):242-50. · 16.10 Impact Factor
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ABSTRACT: Cystinosis is a rare autosomal recessive disorder due to impaired transport of cystine out of cellular lysosomes. Its estimated incidence is 1 in 100,000 live births. End-stage renal disease (ESRD) is the most prominent feature of cystinosis and, along with dehydration and electrolyte imbalance due to renal tubular Fanconi syndrome, has accounted for the bulk of deaths from this disorder. Prior to renal transplantation and cystine-depleting therapy with cysteamine for children with nephropathic cystinosis, their lifespan was approximately 10 years. Now, cystinotic patients have survived through their fifth decade, but the unremitting accumulation of cystine has created significant non-renal morbidity and mortality. In this article we review the classic presentation of nephropathic cystinosis and the natural history, diagnosis, and treatment of the disorder's systemic involvement. We also emphasize the role of oral cysteamine therapy in preventing the late complications of cystinosis.Pediatric Nephrology 12/2007; 23(6):863-78. DOI:10.1007/s00467-007-0650-8 · 2.88 Impact Factor