Benefitting the Cystinosis Research Network, In Honor of Alexis and Evan LeBeau
Copyright 2007. Cystinosis Research Network.
All rights reserved.
All rights reserved.
Cystinosis is a rare disease that primarily affects children. Cystinosis is a genetic metabolic disease that causes an amino acid, cystine, to accumulate in various organs of the body. Cystine crystals accumulate in the kidneys, eyes, liver, muscles, pancreas, brain and white blood cells. Without specific treatment, children with cystinosis develop end stage kidney failure at approximately age nine.
Cystinosis also causes complications in other organs of the body. The complications include muscle wasting, difficulty swallowing, diabetes, and hypothyroidism. It is estimated that at least 2,000 individuals worldwide have cystinosis, thought exact numbers are difficult to obtain because the disease is often undiagnosed and/ or misdiagnosed.
Cystagon, new treatments, and research of Cystinosis are giving hope for a bright future for children and adults with Cystinosis. Over the last 20 years, the prognosis of a child born with Cystinosis has greatly improved. Scientists have mapped the Cystinosis gene, CTNS, to chromosome 17p13. The researchers reported that the locus D17S829 was homozygously deleted in 23 out of 70 patients.
Cysteamine (Cystagon) has been approved by the Food and Drug Administration (FDA) for standard treatment of Cystinosis. Cysteamine is a cystine-depleting agents that lowers cystine levels within the cells. Cysteamine has proven effective in delaying or preventing renal failure. Cysteamine also improves growth of children with Cystinosis. In view of the harmful effects of chronic cystine accumulation, and the indications of the effectiveness of Cysteamine therapy in various tissues and organ systems, oral Cysteamine should be used by Post-transplant Cystinosis patients.
Cysteamine eye drops dissolve corneal cystine crystals and relieve photophobia.
There are three forms of Cystinosis. Infantile Nephropathic Cystinosis is the most severe form of the disease. Children with Cystinosis appear normal at birth, but by 10 months of age, they are clearly shorter that others their age. They urinate frequently, have excessive thirst, and often seem fussy. At 12 months, they haven't walked and bear weight only gingerly.
One of the major complications of Cystinosis is renal tubular Fanconi Syndrome, or a failure of the kidneys to reabsorb nutrients and minerals. The minerals are lost in the urine. The urinary losses must be replaced. Generally, they are picky eaters, crave salt, and grow very slowly. If left untreated, this form of the disease may lead to kidney failure by 10 years of age.
In people with Intermediate Cystinosis or Juvenile (adolescent) Cystinosis, kidney and eye symptoms typically become apparent during the teenage years or early adulthood. In Benign or Adult Cystinosis, cystine accumulates primarily in the cornea of the eyes.
TREATMENT OF CYSTINOSIS
Cystinosis is treated symptomatically. Renal tubular dysfunction requires a high intake of fluids and electrolytes to prevent excessive loss of water from the body (dehydration). Sodium bicarbonate, sodium citrate, and potassium citrate may be administered to maintain the normal electrolyte balance. Phosphates and vitamin D are also required to correct the impaired uptake of phosphate into the kidneys and to prevent rickets. Carnitine may help to replace muscular carnitine deficiency.
Cysteamine (Cystagon) has been approved by the Food and Drug Administration (FDA) for standard treatment of Cystinosis. Cysteamine is a cystine-depleting agents that lowers cystine levels within the cells. Cysteamine has proven effective in delaying or preventing renal failure. Cysteamine also improves growth of children with Cystinosis. In view of the harmful effects of chronic cystine accumulation, and the indications of the effectiveness of Cysteamine therapy in various tissues and organ systems, oral Cysteamine should be used by Post-transplant Cystinosis patients.
Cysteamine eye drops dissolve corneal cystine crystals and relieve photophobia.
HOW IS CYSTINOSIS INHERITED?
Every person's body is made up of millions of tiny structures called cells. Each cell comes with a full set of instructions which tell the cell what to do and how to make our bodies work. The instructions are called genes, and they are made from a chemical called DNA. Genes usually come in pairs, and they determine everything about our bodies. For example, certain genes determine the color of our eyes, while other genes determine our blood type.
Genes are often called the units of heredity because the information they contain is passed from one generation to the next. We all get one gene in each pair from our mothers and the other gene in the pair from our fathers. In this way our bodies work with a combination of instructions inherited from both our parents. Parents have no control over which genes get passed to their children.
Cystinosis is called a recessive genetic disease, because parents do not exhibit symptoms, but they each carry a recessive gene which may cause Cystinosis in their children. The genetic path of Cystinosis is therefore impossible to predict, and a cystinotic child is almost always a shock to parents. The recessive gene may lie dormant for many generations until suddenly two people with the defective gene have children.
Each time two such Cystinosis carrier have a child together, there is a1-in-4 chance (25% risk) of having a child with Cystinosis. and every healthy sibling of a child with Cystinosis has a 2-in-3 chance (66% risk) of being a carrier, like his parents.
References
National Organization for Rare Disorders, Rare Disease Database, Cystinosis, 1997.
Cystinosis Foundation, Inc., Brochure, 1997.
Mendelian Inheritance in Man, 10th Ed.: Victor A. McKusick, Editor: Johns Hopkins University Press, 1992. Pp. 92-92.
Online Mendelian Inheritance in Man (OMIM). Victor A. McKusick, Editor, Johns Hopkins University; last edit date 8/19/94, Entry Number219800; last edit date 2/19/94, Entry Number 219900; last edit date 2/19/94, Entry Number 219750.
The Metabolic Basis of Inherited Disease, 6th Ed.: Charles R. Scriver et al., Editors; McGraw Hill, 1989. Pp.2619-2635.
Birth Defects Encyclopedia: Mary Louise Buyse, M.D., Editor-In-Chief, Blackwell Scientific Publications, 1990. Pp. 482-483.
The Kidney, 4th Ed.: Barry M. Brenner, M.D. and Floyd C. Rector, Jr., M.D., Editors; W.B. Saunders Company, 1991. Pp. 1618, 1758.
NIH Conference. Cystinosis: Progress in a Prototypic Disease: W.A. Gahl, J.G. Thoene et al.; Ann Intern Med (Oct 1988; 109(7)). Pp. 557-69.
Improved Renal Function in Children with Cystinosis Treated with Cysteamine. T. C. Markello et al.; N Engl J Med (Apr 22, 1993; 328(16)). Pp. 1157-62.
Growth and Pubertal Development in Nephropathic Cystinosis. L. Winkler et al.: Eur J Pediatr (Mar 1993; 152(3)). Pp.244-49.
Renal Transplantation for Infantile Cystinosis: Long Tern Follow-Up. P.S. Almond et al.; J Pediatric Surg (Feb 1993; 28(2)). Pp. 232-38.
Muscle Carnitine Repletion by Long-Term Carnitine Supplementation in Nephropathic Cystinosis. W.A. Gahl et al.; Pediatr Res (Aug 1993; 34(2)). Pp. 115-19.
Nature Genetics; 18:319-324
Cystinosis also causes complications in other organs of the body. The complications include muscle wasting, difficulty swallowing, diabetes, and hypothyroidism. It is estimated that at least 2,000 individuals worldwide have cystinosis, thought exact numbers are difficult to obtain because the disease is often undiagnosed and/ or misdiagnosed.
Cystagon, new treatments, and research of Cystinosis are giving hope for a bright future for children and adults with Cystinosis. Over the last 20 years, the prognosis of a child born with Cystinosis has greatly improved. Scientists have mapped the Cystinosis gene, CTNS, to chromosome 17p13. The researchers reported that the locus D17S829 was homozygously deleted in 23 out of 70 patients.
Cysteamine (Cystagon) has been approved by the Food and Drug Administration (FDA) for standard treatment of Cystinosis. Cysteamine is a cystine-depleting agents that lowers cystine levels within the cells. Cysteamine has proven effective in delaying or preventing renal failure. Cysteamine also improves growth of children with Cystinosis. In view of the harmful effects of chronic cystine accumulation, and the indications of the effectiveness of Cysteamine therapy in various tissues and organ systems, oral Cysteamine should be used by Post-transplant Cystinosis patients.
Cysteamine eye drops dissolve corneal cystine crystals and relieve photophobia.
There are three forms of Cystinosis. Infantile Nephropathic Cystinosis is the most severe form of the disease. Children with Cystinosis appear normal at birth, but by 10 months of age, they are clearly shorter that others their age. They urinate frequently, have excessive thirst, and often seem fussy. At 12 months, they haven't walked and bear weight only gingerly.
One of the major complications of Cystinosis is renal tubular Fanconi Syndrome, or a failure of the kidneys to reabsorb nutrients and minerals. The minerals are lost in the urine. The urinary losses must be replaced. Generally, they are picky eaters, crave salt, and grow very slowly. If left untreated, this form of the disease may lead to kidney failure by 10 years of age.
In people with Intermediate Cystinosis or Juvenile (adolescent) Cystinosis, kidney and eye symptoms typically become apparent during the teenage years or early adulthood. In Benign or Adult Cystinosis, cystine accumulates primarily in the cornea of the eyes.
TREATMENT OF CYSTINOSIS
Cystinosis is treated symptomatically. Renal tubular dysfunction requires a high intake of fluids and electrolytes to prevent excessive loss of water from the body (dehydration). Sodium bicarbonate, sodium citrate, and potassium citrate may be administered to maintain the normal electrolyte balance. Phosphates and vitamin D are also required to correct the impaired uptake of phosphate into the kidneys and to prevent rickets. Carnitine may help to replace muscular carnitine deficiency.
Cysteamine (Cystagon) has been approved by the Food and Drug Administration (FDA) for standard treatment of Cystinosis. Cysteamine is a cystine-depleting agents that lowers cystine levels within the cells. Cysteamine has proven effective in delaying or preventing renal failure. Cysteamine also improves growth of children with Cystinosis. In view of the harmful effects of chronic cystine accumulation, and the indications of the effectiveness of Cysteamine therapy in various tissues and organ systems, oral Cysteamine should be used by Post-transplant Cystinosis patients.
Cysteamine eye drops dissolve corneal cystine crystals and relieve photophobia.
HOW IS CYSTINOSIS INHERITED?
Every person's body is made up of millions of tiny structures called cells. Each cell comes with a full set of instructions which tell the cell what to do and how to make our bodies work. The instructions are called genes, and they are made from a chemical called DNA. Genes usually come in pairs, and they determine everything about our bodies. For example, certain genes determine the color of our eyes, while other genes determine our blood type.
Genes are often called the units of heredity because the information they contain is passed from one generation to the next. We all get one gene in each pair from our mothers and the other gene in the pair from our fathers. In this way our bodies work with a combination of instructions inherited from both our parents. Parents have no control over which genes get passed to their children.
Cystinosis is called a recessive genetic disease, because parents do not exhibit symptoms, but they each carry a recessive gene which may cause Cystinosis in their children. The genetic path of Cystinosis is therefore impossible to predict, and a cystinotic child is almost always a shock to parents. The recessive gene may lie dormant for many generations until suddenly two people with the defective gene have children.
Each time two such Cystinosis carrier have a child together, there is a1-in-4 chance (25% risk) of having a child with Cystinosis. and every healthy sibling of a child with Cystinosis has a 2-in-3 chance (66% risk) of being a carrier, like his parents.
References
National Organization for Rare Disorders, Rare Disease Database, Cystinosis, 1997.
Cystinosis Foundation, Inc., Brochure, 1997.
Mendelian Inheritance in Man, 10th Ed.: Victor A. McKusick, Editor: Johns Hopkins University Press, 1992. Pp. 92-92.
Online Mendelian Inheritance in Man (OMIM). Victor A. McKusick, Editor, Johns Hopkins University; last edit date 8/19/94, Entry Number219800; last edit date 2/19/94, Entry Number 219900; last edit date 2/19/94, Entry Number 219750.
The Metabolic Basis of Inherited Disease, 6th Ed.: Charles R. Scriver et al., Editors; McGraw Hill, 1989. Pp.2619-2635.
Birth Defects Encyclopedia: Mary Louise Buyse, M.D., Editor-In-Chief, Blackwell Scientific Publications, 1990. Pp. 482-483.
The Kidney, 4th Ed.: Barry M. Brenner, M.D. and Floyd C. Rector, Jr., M.D., Editors; W.B. Saunders Company, 1991. Pp. 1618, 1758.
NIH Conference. Cystinosis: Progress in a Prototypic Disease: W.A. Gahl, J.G. Thoene et al.; Ann Intern Med (Oct 1988; 109(7)). Pp. 557-69.
Improved Renal Function in Children with Cystinosis Treated with Cysteamine. T. C. Markello et al.; N Engl J Med (Apr 22, 1993; 328(16)). Pp. 1157-62.
Growth and Pubertal Development in Nephropathic Cystinosis. L. Winkler et al.: Eur J Pediatr (Mar 1993; 152(3)). Pp.244-49.
Renal Transplantation for Infantile Cystinosis: Long Tern Follow-Up. P.S. Almond et al.; J Pediatric Surg (Feb 1993; 28(2)). Pp. 232-38.
Muscle Carnitine Repletion by Long-Term Carnitine Supplementation in Nephropathic Cystinosis. W.A. Gahl et al.; Pediatr Res (Aug 1993; 34(2)). Pp. 115-19.
Nature Genetics; 18:319-324
