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$Unique_ID{BRK03645}
$Pretitle{}
$Title{Cystinosis}
$Subject{Cystinosis Cystine Storage Disease Fanconi II Lignac-Fanconi Syndrome
INFANTILE CYSTINOSIS: Nephropathic Cystinosis Infantile Fanconi Syndrome with
Cystinosis Dwarfism with Rickets de Toni-Fanconi Syndrome
Abderhalden-Kaufmann-Lignac Syndrome Lignac-Debre-Fanconi Syndrome
Nephrotic-Glycosuric-Dwarfism-Rickets-Hypophosphatemic Syndrome,
Aminoaciduria-Osteomalacia-Hyperphosphaturia Syndrome ADOLESCENT CYSTINOSIS
(Intermediate Cystinosis and Juvenile Cystinosis) Adult Cystinosis (Benign
Cystinosis) Fanconi Syndrome (Renal)}
$Volume{}
$Log{}

Copyright (C) 1986, 1987, 1988, 1990, 1991, 1993 National Organization
for Rare Disorders, Inc.

59:
Cystinosis

** IMPORTANT **
It is possible that the main title of the article (Cystinosis) is not the
name you expected.  Please check the SYNONYMS listing to find the alternate
name and disorder subdivisions covered by this article.

Synonyms

     Cystine Storage Disease
     Fanconi II
     Lignac-Fanconi Syndrome

DISORDER SUBDIVISIONS:

INFANTILE CYSTINOSIS:

     Nephropathic Cystinosis
     Infantile Fanconi Syndrome with Cystinosis
     Dwarfism with Rickets
     de Toni-Fanconi Syndrome
     Abderhalden-Kaufmann-Lignac Syndrome
     Lignac-Debre-Fanconi Syndrome
     Nephrotic-Glycosuric-Dwarfism-Rickets-Hypophosphatemic Syndrome,
and Aminoaciduria-Osteomalacia-Hyperphosphaturia Syndrome

ADOLESCENT CYSTINOSIS (Intermediate Cystinosis and Juvenile Cystinosis)

Adult Cystinosis (Benign Cystinosis)

Information on the following diseases can be found in the Related
Disorders section of this report:

     Fanconi Syndrome (Renal)

General Discussion

** REMINDER **
The Information contained in the Rare Disease Database is provided for
educational purposes only.  It should not be used for diagnostic or treatment
purposes.  If you wish to obtain more information about this disorder, please
contact your personal physician and/or the agencies listed in the "Resources"
section of this report.


Cystinosis is an inherited disorder of the transport of cystine out of
parts of cells called lysosomes.  Lysosomes are particles bound in membranes
within cells.  Cystine is an amino acid found in many proteins in the body.
This disorder is characterized by the accumulation of cystine in tissues
throughout the body, which can cause certain organs to malfunction.

Three forms of Cystinosis are recognized.  Infantile Nephropathic
Cystinosis is the most severe form of the disease.  Symptoms can appear as
early as 6 to 12 months of age and if left untreated, may lead to kidney
failure by 10 years of age.  In benign (or adult) Cystinosis, crystalline
cystine accumulates primarily in the cornea of the eyes.  In people with the
intermediate form of Cystinosis (also called juvenile or adolescent
Cystinosis), kidney and eye symptoms are apparent in the teens or twenties.

One of the major complications of Cystinosis is the renal fanconi
syndrome.  (See the related disorders section of this report for information
about Renal Fanconi Syndrome.)

Symptoms

People with Cystinosis accumulate excessive amounts of cystine in the
lysosomes of all tissues.  The early symptoms of this disorder typically
involve the kidneys and eyes.  Individuals with Cystinosis have six-sided
(hexagonal) or rectangular cystine crystals present in their bone marrow
samples (aspirates), white blood cells (leukocytes), and/or the membranes
that line the rectum (rectal mucosa).  These crystals are also found in the
corneas and membranes that line the eyes (conjunctiva).

People who have inherited only one gene of a pair that causes Cystinosis
(heterozygotes) have slightly elevated levels of intracellular cystine, but
no symptoms.  People with two genes that cause Cystinosis will have symptoms.
Cystine accumulation in the kidneys impairs the ability of the kidneys to
save mineral salts, causing abnormally low levels of sodium, potassium and
phosphate in the blood.  It also causes excessive urination (polyuria) and
excessive thirst (polydipsia).  These conditions together comprise the Renal
Fanconi Syndrome.  The accumulation of cystine crystals in the cornea and
conjunctiva of the eyes may cause an increased sensitivity to light
(photophobia), headaches, and itching and/or burning of the eyes.  A
physician is able to see crystals in the cornea of the eyes through a slit-
lamp examination.

The symptoms of Infantile Nephropathic Cystinosis typically appear before
the age of 1 year.  Infants with this disorder usually have a patchy loss of
color (depigmentation) in the retina of the eyes and an abnormal sensitivity
to light (photophobia).  Hypophosphatemic Vitamin D-Resistant rickets
(abnormal bone formation) may occur, as well as poor growth; the child fails
to thrive and is pale and thin.  The bones may be soft, and result in
deformities that appear as the child grows older.  Untreated Cystinosis leads
to kidney (glomerular) failure by 10 years of age.  (For more information on
Vitamin D-Resistant Rickets, choose "Rickets" as your search term in the Rare
Disease Database.)

The symptoms of kidney dysfunction associated with Intermediate or
Juvenile Cystinosis resemble those of the infantile form of the disease, but
are generally milder.   Abnormal bone formation (Rickets) sometimes occurs.

The adult form of Cystinosis is typically benign.  This form of the
disease is primarily characterized by crystals in the corneas of the eyes.
Ocular itching and burning may also occur, but kidney function remains
intact.

Causes

Cystinosis is inherited as an autosomal recessive genetic trait.  Human
traits, including the classic genetic diseases, are the product of the
interaction of two genes, one received from the father and one from the
mother.  In recessive disorders, the condition does not appear unless a
person inherits the same defective gene for the same trait from each parent.
If one receives one normal gene and one gene for the disease, the person will
be a carrier for the disease, but usually will not show symptoms.  The risk
of transmitting the disease to the children of a couple, both of whom are
carriers for a recessive disorder, is twenty-five percent.  Fifty percent of
their children will be carriers, but healthy as described above.  Twenty-five
percent of their children will receive both normal genes, one from each
parent, and will be genetically normal.

Affected Population

Cystinosis is a rare disorder that affects males and females in equal
numbers.  Approximately 200 cases have been identified in the United States.

Related Disorders

Symptoms of the following disorders can be similar to those of Cystinosis.
Comparisons may be useful for a differential diagnosis:

The renal fanconi syndrome is a rare disorder characterized by abnormal
kidney function (proximal tubular), particularly involving excessive
excretion of glucose, phosphates, amino acids, bicarbonate, water, potassium,
calcium, sodium, and carnitine.  Other symptoms of this disorder may include
abnormally low levels of potassium in the blood (hypokalemia), excessive
urination (polyuria), excessive thirst (polydipsia), and/or abnormally low
levels of phosphate in the blood (hypophosphatemia).  The renal fanconi
syndrome may be, besides nephropathic Cystinosis, associated with other
hereditary metabolic conditions including tyrosinemia, galactosemia, fructose
intolerance, glycogen storage disease type I, Wilson Disease, familial
Nephrosis, and Lowe Syndrome.  The onset of the renal fanconi syndrome is
also associated with the use of certain aminoglycosides and outdated
tetracycline.  It has been associated with poisoning by heavy metals or other
chemicals.

Therapies:  Standard

Benign forms of Cystinosis require little or no treatment.

Nephropathic 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 required to correct
the impaired resorption of phosphate into the kidneys (hypophosphatemia) and
prevent rickets.

Hemodialysis or kidney transplantation is required in end stage renal
disease.  Kidney transplantation is successful in this condition, however
linear growth does not improve.

Corneal transplantation has been successfully performed in Cystinosis
patients using related donors.

Cystinosis can be detected during pregnancy by a special obstetric
procedure in which a small amount of amniotic fluid is removed for laboratory
analysis (amniocentesis).  In another prenatal procedure, chorionic villus
sampling, a small amount of tissue from the placenta is removed and examined.

Genetic counseling will be of benefit for patients and their families.


Therapies:  Investigational

Cysteamine and phosphocysteamine, which are both cystine depleting agents,
are being investigated for the treatment of Cystinosis.  These two drugs
lower cystine levels within cells.  Cysteamine has a strong, unpleasant odor,
a disadvantage that phosphocysteamine lacks.  For more information patients
may wish to have their physicians contact:  Jess Thoene, M.D., University of
University of Michigan, Ann Arbor, MI, 48109

This disease entry is based upon medical information available through
June 1993.  Since NORD's resources are limited, it is not possible to keep
every entry in the Rare Disease Database completely current and accurate.
Please check with the agencies listed in the Resources section for the most
current information about this disorder.

Resources

For more information on Cystinosis, please contact:

     National Organization for Rare Disorders (NORD)
     P.O. Box 8923
     New Fairfield, CT  06812-1783
     [phone]

     Cystinosis Foundation, Inc.
     17 Lake Ave.
     Piedmont, CA  94611
     [phone]
     [phone]

     National Kidney and Urologic Diseases Information Clearinghouse
     Box NKUDIC
     Bethesda, MD  20892
     [phone]

     Research Trust for Metabolic Diseases in Children
     Golden Gate Lodge, Weston Road
     Crewe CW1 1XN, England
     Telephone:  [phone]

     Jerry Schneider, M.D.
     University of California at San Diego
     9500 Gilman Drive
     La Jolla, CA  92093

For Genetic Information and Genetic Counseling Referrals:

     March of Dimes Birth Defects Foundation
     1275 Mamaroneck Ave.
     White Plains, NY  10605
     [phone]

     Alliance of Genetic Support Groups
     35 Wisconsin Circle, Suite 440
     Chevy Chase, MD  20815
     (800) 336-GENE
     [phone]

References

MENDELIAN INHERITANCE IN MAN, 10th Ed.:  Victor A. McKusick, Editor:  Johns
Hopkins University Press, 1992.  Pp. 92-94.

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.