OVERVIEW

PRODUCT INFORMATION

CHEMICAL FORMULA AND STRUCTURE

View in own window

DRUG	CAS REGISTRY NO.	MOLECULAR FORMULA	STRUCTURE
Cysteamine	27761-19-9	C4-H6-O6.C2-H7-N-S

ANNOTATED BIBLIOGRAPHY

References updated: 03 November 2017

• Zimmerman, HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999: pp. 731-4.

  (Expert review of hepatotoxicity published in 1999; cysteamine is not discussed).
• Gahl WA, Bashan N, Tietze F, Bernardini I, Schulman JD. Cystine transport is defective in isolated leukocyte lysosomes from patients with cystinosis. Science 1982; 217 (4566): 1263-5. [PubMed: 7112129]

  (Demonstration of defective transporter for cystine in lysosomes from patients with cystinosis which results in a toxic accumulation of cystine; in contrast, the egress of methionine, tryptophan and other amino acids is normal, suggesting a specific amino acid transporter defect).
• Avner ED, Ellis D, Jaffee R. Veno-occlusive disease of the liver associated with cysteamine treatment of nephropathic cystinosis. J Pediatr 1983; 102: 793-6. [PubMed: 6842343]

  (8 year old boy with nephropathic cystinosis developed ascites and gastrointestinal bleeding from gastric varices 22 months after starting cysteamine [bilirubin not given, ALT 16 U/L, Alk P 68 U/L, protime 19 sec], biopsy showing changes of sinusoidal obstruction syndrome).
• Gahl WA, Schulman JD, Thoene JG, Schneider J. Hepatotoxicity of cysteamine? J Pediatr 1983; 103: 1008-9. [PubMed: 6644413]

  (Letter in response to Avner [1983] suggesting that sinusoidal obstruction syndrome may be a part of the clinical spectrum of cystinosis, rather than a complication of cysteamine therapy).
• Gahl WA, Schneider JA, Thoene JG, Chesney R. Course of nephropathic cystinosis after age 10 years. J Pediatr 1986; 109: 605-8. [PubMed: 3531450]

  (Among 80 patients with nephropathic cystinosis above the age of 10 identified in a US wide survey, 90% had undergone renal transplant [at an average age of 10 years] and the oldest child without transplant was 14 and on dialysis; other complications included hepatomegaly [42%] and splenomegaly, but liver tests were abnormal in only 11 [14%] who had mild ALT or AST elevations; other late complications included photophobia, decreased visual acuity and hypothyroidism).
• Gahl WA, Reed GF, Thoene JG, Schulman JD, Rizzo WB, Jonas AJ, Denman DW, et al. Cysteamine therapy for children with nephropathic cystinosis. N Engl J Med 1987; 316: 971-7. [PubMed: 3550461]

  (Among 93 children with nephropathic cystinosis treated with cysteamine hydrochloride [mean dose 51 mg/kg daily] for up to 6 years, leucocyte cystine concentrations decreased by 82%, renal function stabilized and growth was improved in comparison to historical controls who were not treated; side effects included nausea [from its taste and odor] and one child developed sinusoidal obstruction syndrome which was attributed to the underlying disease, rather than cysteamine).
• Gahl WA, Thoene JG, Schneider JA, O'Regan S, Kaiser-Kupfer MI, Kuwabara T. NIH conference. Cystinosis: progress in a prototypic disease. Ann Intern Med 1988; 109: 557-69. [PubMed: 3048161]

  (Review of the clinical characteristics, epidemiology, pathogenesis, complications and therapy of cystinosis).
• Kimonis VE, Troendle JR, Rose SR, Yang ML, Markello TC, Gahl WA. Effects of early cysteamine therapy on thyroid function and growth in nephropathic cystinosis. J Clin Endocrinol Metab 1995; 80: 3257-61. [PubMed: 7593434]

  (Among 101 patients with nephropathic cystinosis treated with cysteamine, those started on therapy before the age of 2 and who maintained optimal leukocyte cystine levels [n=24] had lower rates of hypothyroidism and better growth and bone age than those with partial [n=36] or poor or delayed [n=47] treatment responses).
• Gahl WA, Thoene JG, Schneider JA. Cystinosis. N Engl J Med 2002; 347: 111-21. [PubMed: 12110740]

  (Review of the history, clinical characteristics, clinical variants, complications, genetics, diagnosis and treatment of cystinosis).
• Kleta R, Gahl WA. Pharmacological treatment of nephropathic cystinosis with cysteamine. Expert Opin Pharmacother 2004; 5: 2255-62. [PubMed: 15500372]

  (Review of cysteamine therapy of cystinosis; states that early diagnosis and therapy with cysteamine can guarantee normal growth and maintenance of renal function).
• Kleta R, Bernardini I, Ueda M, Varade WS, Phornphutkul C, Krasnewich D, Gahl WA. Long-term follow-up of well-treated nephropathic cystinosis patients. J Pediatr 2004; 145: 555-60. [PubMed: 15480385]

  (Long term course of two siblings with cystinosis who were started on cysteamine therapy at 2 and 20 months of age, and both achieved normal growth and maintained normal renal function [creatinine clearance of 78 and 105 mL/min] for 8 and 12 years).
• Kleta R, Kaskel F, Dohil R, Goodyer P, Guay-Woodford LM, Harms E, Ingelfinger JR, et al.; NIH Office of Rare Diseases. First NIH/Office of Rare Diseases Conference on Cystinosis: past, present, and future. Pediatr Nephrol 2005; 20: 452-4. [PubMed: 15747161]

  (Brief summary of the major clinical challenges in cystinosis including early diagnosis, improved therapeutics, better compliance and transition of care from pediatric to adult medical services).
• O'Brien K, Hussain N, Warady BA, Kleiner DE, Kleta R, Bernardini I, Heller T, et al. Nodular regenerative hyperplasia and severe portal hypertension in cystinosis. Clin Gastroenterol Hepatol 2006; 4: 387-94. [PubMed: 16527704]

  (Two adults, ages 19 and 30 years, with nephropathic cystinosis but minimal exposure to cysteamine were found to have severe noncirrhotic portal hypertension, and liver biopsies demonstrated nodular regenerative hyperplasia with minimal portal fibrosis, the etiology of which was unknown).
• Gahl WA, Balog JZ, Kleta R. Nephropathic cystinosis in adults: natural history and effects of oral cysteamine therapy. Ann Intern Med 2007; 147: 242-50. [PubMed: 17709758]

  (Among 100 adults with nephropathic cystinosis, 92 had a kidney transplants and at least half had hypothyroidism, hypergonadism, pulmonary insufficiency, swallowing disorders and myopathy, one-third had retinopathy and one quarter diabetes; cysteamine therapy was associated with delay in need for renal allograft and fewer complications and deaths).
• Bendel-Stenzel MR, Steinke J, Dohil R, Kim Y. Intravenous delivery of cysteamine for the treatment of cystinosis: association with hepatotoxicity. Pediatr Nephrol 2008; 23: 311-5. [PubMed: 17668247]

  (Two year old girl with severe nephropathic cystinosis and intolerance to oral cysteamine was treated with an intravenous form [5-6 mg/kg every 8 hours] which resulted in decreases in intracellular cystine, but was followed after 50 days by marked elevations in serum ALT [2117 U/L] and AST [1362 U/L] without jaundice [bilirubin 0.4 mg/dL], levels promptly falling on stopping the infusions and recurring with intravenous rechallenge [ALT ~140 U/L after 25 days], and later with oral rechallenge using cysteamine bitartrate [ALT 249 U/L after 6 months]).
• Besouw MT, Bowker R, Dutertre JP, Emma F, Gahl WA, Greco M, Lilien MR, et al. Cysteamine toxicity in patients with cystinosis. J Pediatr 2011; 159: 1004-11. [PubMed: 21784456]

  (Among 550 European patients with cystinosis who were treated with cysteamine, 8 developed possible toxicity, 6 of whom developed vascular lesions over the elbow marked by irregular collagen fibers and angioendotheliomatosis, other complications were leg pains and neurologic symptoms which improved with lowering the dose; possibly due to inhibition of cross linking of collagen).
• Dohil R, Schmeltzer S, Cabrera BL, Wang T, Durelle J, Duke KB, Schwimmer JB, et al. Enteric-coated cysteamine for the treatment of paediatric non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2011; 33: 1036-44. [PubMed: 21395631]

  (Among 11 children [>10 years] with nonalcoholic fatty liver disease and raised serum ALT levels treated with enteric coated cysteamine [15 mg/kg daily], mean ALT levels fell [from 120 to 55 U/L], with no change in weight and rise of ALT values after stopping therapy [to 74 U/L).
• Langman CB, Greenbaum LA, Sarwal M, Grimm P, Niaudet P, Deschênes G, Cornelissen E, et al. A randomized controlled crossover trial with delayed-release cysteamine bitartrate in nephropathic cystinosis: effectiveness on white blood cell cystine levels and comparison of safety. Clin J Am Soc Nephrol 2012; 7: 1112-20. [PMC free article: PMC3386675] [PubMed: 22554716]

  (Among 43 patients with cystinosis treated with standard cysteamine [every 6 hours] or a new formulation of enteric coated, delayed release form of cysteamine bitartrate [every 12 hours] for 3 weeks with subsequent cross over, mean peak white cell cystine levels were similar, but gastrointestinal side effects were greater with the delayed release form).
• Schwimmer JB, Lavine JE, Wilson LA, Neuschwander-Tetri BA, Xanthakos SA, Kohil R, Barlow S, et al. In children with nonalcoholic fatty liver disease, cysteamine bitartrate delayed-release improves liver enzymes but does not reduce disease activity scores. Gastroenterol 2016: 151: 1141-54. [PMC free article: PMC5124386] [PubMed: 27569726]

  (Among 169 children with nonalcoholic fatty liver treated with cysteamine [150 to 450 mg daily] or placebo for 48 weeks, ALT and AST levels improved significantly, but histologic changes were minimal; no patient developed clinically worsening or clinically apparent liver injury).