mclogo.gif (4379 bytes)

The Montreal Children's Hospital
Division of Pediatric Nephrology
UN HOPITAL D'ENSEIGNEMENT        McGILL UNIVERSITY         A TEACHING HOSPITAL    
Centre universitaire de santé (CUSM) McGill University Health Centre (MUHC)

muhc_c_s.gif (1661 bytes)

                                                               

[Under Construction]

 

Cystinosis 

Cystinosis is an inherited metabolic disorder first recognized in the 1930’s by Fanconi.  In children who inherit two mutant cystinosis genes from their parents, cystine accumulates in cells throughout the body causing progressive tissue damage.   The problem is especially severe in the kidney causing tubular dysfunction in the first years of life and advanced renal failure by the end of the first decade of life. The incidence in Quebec is about ten times higher than in the rest of North America and is an important cause of kidney failure in our pediatric population.

 Two important breakthroughs may change the outlook for these children. Capitalizing on laboratory observations by  Goldman and Scriver at the Montreal Children’s Hospital, two US physicians, Drs. Gahl and Schneider, introduced cysteamine as a new treatment for cystinosis.  In a large multicenter North American trial which included many Quebec families, it was shown that oral cysteamine rapidly lowers the level of cystine in white blood cells and reduces the rate of progressive renal failure in children where the treatment is given regularly from early infancy (New England Journal of Medicine, 328:1157-1162, 1993).  The Montreal Children’s Hospital currently serves as a Canadian reference center for monitoring white blood cell cystine levels during cysteamine therapy.

 In the spring of 1998, Antignac and an international group from France, England and Australia announced the isolation of the cystinosis gene (Nature Genetics 18:319-324, 1998).   This accomplishment is likely to help us understand which patients will have the worst outcomes and will, hopefully, open the door to gene therapy in the future.    We are currently collaborating with Dr. Alex MacKenzie (Children’s Hospital of Eastern Ontario) who is analyzing patient DNA samples for cystinosis gene mutations in an effort to determine whether there are mild, moderate and severe forms of cystinosis in the Canadian population.

 Cystinosis patients are followed in the Renal Genetics Clinic at the Montreal Children’s Hospital.   All patients are offered therapy with cysteamine and close monitoring of white blood cell cystine levels.  Children who already have advanced renal failure are also offered cysteamine therapy since it is thought to be protective for other tissues including the thyroid gland and pancreas and bone marrow.  Dialysis and transplantation services are available to children with advanced renal failure – survival of the transplanted kidney is excellent in cystinosis patients.  Ongoing clinical studies at our hospital are designed to improve nutrition and growth, and to optimize the success of renal transplantation if needed.