Nephropathic cystinosis

Cysteamine (/3-mercapto-ethylamine) is used for the treatment of nephropathic cystinosis. Cysteamine converts within lysosomes cystine into cysteine and cysteine-cysteamine mixed disulfide, both of which can exit the lysosome thus removing the extra cystine. After oral administration peak plasma levels are reached at about 1.4 hours post dose. It is eliminated as a sulfate in the urine with a half-life of 4-5 hours. The most frequent adverse reactions seen involve the gastrointestinal and central nervous systems. Side effects include abdominal pain, diarrhea, drowsiness, fever, loss of appetite, nausea or vomiting and skin rash. Confusion, dizziness and headache may occur. 

Gahl WA, Balog JZ, Kleta R. Nephropathic cystinosis in adults natural history and effects of oral cysteamine therapy. Ann Intern Med 2007 147(4) 242-50. 

Wuhl E, Haffner D, Offner G, Broyer M, van t Hoff W, Mehls OEuropean Study Group on Growth Hormone Treatment in Children with Nephropathic Cystinosis. Long-term treatment with growth hormone in short children with nephropathic cystinosis. J Pediatr 2001 138(6) 880-7. 

An 8-year-old boy with nephropathic cystinosis had debilitating and worsening photophobia from corneal crystal deposition (3). After 8 months of topical application of mercaptamine, he has marked improvement, both subjectively and objectively. 

In 93 children with nephropathic cystinosis oral mercaptamine 51 mg/kg for up to 73 months produced 82% cystine depletion from leukocytes and improved creatinine clearance and growth (8). However, 14% of the patients could not tolerate the taste and smell of mercaptamine, which is excreted in the breath. 

In four children with nephropathic cystinosis receiving mercaptamine 14.35 mg/kg qds serum gastrin concentrations up to 90 minutes later rose as did gastric acid output (10). Two of the four subjects had visual and histological evidence of gastric inflammation. The clinical effect of this acid production is unknown. 

Gahl WA. Early oral cysteamine therapy for nephropathic cystinosis. Eur J Pediatr 2003 162(Suppl 1) S38-41. 

Corden BJ, Schulman JD, Schneider JA, Thoene JG. Adverse reactions to oral cysteamine use in nephropathic cystinosis. Dev Pharmacol Ther 1981 3(l) 25-30. 

Gahl WA, Ingelfinger J, Mohan P, Bernardini I, Hyman PE, Tangerman A. Intravenous cysteamine therapy for nephropathic cystinosis. Pediatr Res 1995 38(4) 579-84. 

Gahl WA, Reed GF, Thoene JG, Schulman JD, Rizzo WB, Jonas AJ, Denman DW, Schlesselman JJ, Corden BJ, Schneider JA. Cysteamine therapy for children with nephropathic cystinosis. N Engl J Med 1987 316(16) 971-7. 

MacDonald I M, Noel L P, Mintsioulis G, et al. (1990). The effect of topical cysteamine drops on reducing crystal formation within the cornea of patients affected hy nephropathic cystinosis. J Pediatr Ophthalmol Strabismus 27 272-274. 

Three subtypes of the disease have been differentiated (1) infantile, nephropathic cystinosis (2) late onset or adolescent type cystinosis and (3) adult or benign, non-nephropathic cystinosis. However only adult or benign cystinosis is clearly distinct from the nephropathic forms by the absence of nephropathy. The clinical appearance of nephropathic forms of cytinosis is not uniform but varies among all patients especially in the extent of tubular dysfunction. 

In nephropathic cystinosis clinical chemistry of blood and urine reveals Fanconi syndrome with glucosuria, generalized hyperaminoaciduria and hyperphosphaturia. Most patients show polyuria and loose potassium and bicarbonate resulting in hypokalemia and renal acidosis. Additional tubular losses of calcium, magnesium and carnitine might also occur. The degree of tubular dysfunction is variable in any patient, but also dependent upon... 

L2 Adolescent nephropathic cystinosis (lysosomal membrane cystine transporter) generalized 17p 219900... 

Forestier L, Jean G, Attard M, Cherqui S, Lewis C, van t Hoff W, Broyer M, Town M, Antignac C. Molecular characterization of CTNS deletions in nephropathic cystinosis develeopment of a PCR-based detection assay. Am. J. Hum Genetic 1999 65 353-359... 

A girl with nephropathic cystinosis was given cysteamine bitartrate 30 5 mg/kg/day. However, despite adequate intracellular cystine depletion, her renal function declined and she was given enalapril for proteinuria. When she was 14 years old she was found to have a persistently positive lupus anticoagulant with anticardiolipin, antinuclear, and antihistone antibodies, weakly positive double-stranded DNA antibodies, negative extractable nuclear antibodies, an increased ESR, and low serum complement concentrations. Cysteamine was withdrawn and 1 month later the ESR and complement had fallen and the antibody titers had become weakly positive. 

Nephropathic cystinosis is an autosomal recessive inherited disorder resulting from a defective lysosomal transport of cystine. The cystinosis gene has been mapped to chromosome 17pl3 (Town et al. 1998). Biochemically, the disorder is characterised by intracellular accumulation of cystine in the kidneys and nearly all other organs like the bone marrow, leukocytes, the thyroid gland and the cornea, but the renal symptoms predominate. Affected patients present during infancy with vom-... 

Taylor GA (1994) Comparison of color Doppler amplitude and frequency shift Imaging of children and experimental correlation. Radiology 193 372 Teele RL, Chare JC (1991) Ultrasonography in infants and children. Saunders, Philadelphia Theodoropoulos DS, Shawker TH, Heinrichs C et al (1995) Medullary nephrocalcinosis in nephropathic cystinosis. Pediatr Nephrol 9 412-18... 

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