CD-ROM Today (UK) (Spanish) 15/CDRT.iso/dp/0394/03945.txt

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$Unique_ID{BRK03945}
$Pretitle{}
$Title{Lowe's Syndrome}
$Subject{Lowe's Syndrome Lowe's Disease Oculocerebrorenal Dystrophy
Cerebro-Oculorenal Dystrophy Lowe-Bickel Syndrome Lowe-Terry-Mclachlan
Syndrome Fanconi II Syndrome Cystinuria Glaucoma Cataracts Vitamin D Resistant
Rickets}
$Volume{}
$Log{}

Copyright (C) 1986, 1987, 1989, 1990, 1992, 1993 National Organization
for Rare Disorders, Inc.

109:
Lowe's Syndrome

** IMPORTANT **
It is possible that the main title of the article (Lowe's Syndrome) is
not the name you expected.  Please check the SYNONYM listing to find the
alternate names and disorder subdivisions covered by this article.

Synonyms

     Lowe's Disease
     Oculocerebrorenal Dystrophy
     Cerebro-Oculorenal Dystrophy
     Lowe-Bickel Syndrome
     Lowe-Terry-Mclachlan Syndrome

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

     Fanconi II Syndrome
     Cystinuria
     Glaucoma
     Cataracts
     Vitamin D Resistant Rickets

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.


Lowe's Syndrome is a rare inherited, metabolic disorder characterized by
eye abnormalities such as congenital cataracts and glaucoma, bone
malformations caused by Vitamin D resistant rickets, mental retardation and
impairment of kidney function.

Symptoms

The symptoms of Lowe's Syndrome become apparent in early infancy.  It affects
only males (of all races), but is most common in those with fair coloring.
The muscles may be flabby, the joints unusually flexible (hypermobility) and
there may be little or no muscle reflexes (areflexia).  Other symptoms of
Lowe's Syndrome may include bowed legs (rickets), underdeveloped testes, a
distention of the eyeballs due to fluid buildup (hydropthalmos), cataracts
and glaucoma during infancy, a vertical fold on either side of the nose and
between the eyelids (epicanthal folds), excess fatty tissue, wide ranging
weight and temperature fluctuations, excessive activity level
(hyperactivity), and mental retardation.  There may be a high level of amino
acids (aminoaciduria) and phosphates (phosphaturia) in the urine, a low level
of ammonia, and an impairment of kidney function (tubular acidosis).  The
blood may be slightly acidic, and have elevated nitrogen levels and
electrolyte abnormalities.

Microscopic studies may show abnormalities in the kidneys, testes, eye
and brain.

Female carriers, who have a single gene for the disorder, sometimes have
opacities in the lens of the eye.

Causes

Lowe's Syndrome is a metabolic disorder transmitted through X-linked
recessive genes.  Scientists believe they have located the gene responsible
for the disease.  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.  X-linked recessive disorders are conditions which are
coded on the X chromosome.  Females have two X chromosomes, but males have
one X chromosome and one Y chromosome.  Therefore, in females, disease traits
on the X chromosome can be masked by the normal gene on the other X
chromosome.  Since males only have one X chromosome, if they inherit a gene
for a disease present on the X, it will be expressed.  Men with X-linked
disorders transmit the gene to all their daughters, who are carriers, but
never to their sons.  Women who are carriers of an X-linked disorder have a
fifty percent risk of transmitting the carrier condition to their daughters,
and a fifty percent risk of transmitting the disease to their sons.

In 1992 researchers located the gene on the X chromosome
that causes Lowe's Syndrome.

Prenatal diagnosis of Lowe's Syndrome may be possible with the discovery
of the gene that causes the syndrome as well as a test to determine who is a
carrier of the disease gene.

Affected Population

Lowe's Syndrome is very rare and affects only males.  It is usually
recognized in early infancy.

Related Disorders

Symptoms of the following disorders can be similar to those of Lowe's
Syndrome.  Comparisons may be useful for a differential diagnosis:

Fanconi II Syndrome usually accompanies some other inherited disease,
most commonly the inherited metabolic disease, cystinosis.  It is
characterized by abnormal renal proximal tubular function, particularly in
the reabsorption of glucose, phosphates, amino acids, bicarbonate, uric acid,
water, potassium and sodium.  This form of Fanconi's Syndrome may result from
drug toxicity, kidney transplantation, multiple myeloma and other
malignancies, amyloidosis, certain other hereditary amino acid syndromes, and
certain toxins.  (For more information on this disorder, choose "Cystinosis"
as your search term in the Rare Disease Database).

Cystinuria is an inherited disorder characterized by abnormal intestinal
and kidney transport of the dibasic amino acids cystine, lysine, and
arginine.  This results in excessive amounts of cystine stones in the kidney
and urinary tract.  Cystinuria is the most common of a group of disorders
involving abnormal amino acid transport.  (For more information on this
disorder, choose "Cystinuria" as your search term in the Rare Disease
Database).

The following conditions can be associated with Lowe's Syndrome:

Glaucoma is a disease of the eye characterized by increased intraocular
pressure which results in changes to the optic nerve and may cause blindness.
This disorder tends to occur in older people and is prevalent in the elderly.

Cataracts are abnormalities in the lens of the eye which causes a loss of
transparency (opacity).  They can occur in either one or both eyes, and are
quite common in the elderly.  Congenital cataracts affect babies or young
children and are considered to be a rare birth defect.  Cataracts tend to
cause cloudy vision, and in many cases may result in blindness when left
untreated.

Vitamin D Resistant Rickets is a condition caused by abnormal Vitamin D
metabolism and lower than normal calcium in the blood.  It occurs most often
in infancy and early childhood and is characterized by a bending and
distortion of the bones, a delayed closing of the fontanels of the head, pain
in the muscles and excessive sweating.  (For more information on this
disorder, choose "Vitamin D Resistant Rickets" in the Rare Disease Database.)

Therapies:  Standard

Treatment of Lowe's Syndrome consists of appropriate medications necessary to
reduce or alleviate symptoms and to correct the behavioral and kidney (renal)
problems.

The low level of phosphorus in the blood of males with Lowe's Syndrome is
treated with oral replacement of phosphorus alone, or phosphorus in
combination with Vitamin D to prevent the onset of rickets.  To prevent the
onset of acidosis (accumulation of acid in the blood and bloody tissues), an
alkaline solution is often prescribed.  Surgery or drugs may be considered
for treatment of eye problems such as cataracts and glaucoma; cataracts can
be removed in infancy.  Boys with this disorder may need to wear eyeglasses
or contact lenses.  In some cases, prenatal diagnosis may be possible.
Genetic counseling may be of benefit for patients and their families.  Other
treatment is symptomatic and supportive.

Therapies:  Investigational

At the present time, studies are being conducted on the effectiveness of the
drugs carnitine and thyrocalcitonin as possible treatments of Lowe's
Syndrome.  More research must be conducted to determine long-term safety and
effectiveness of these drugs as a treatment for this disorder.  Researchers at
Cullen Eye Institute of the Baylor College of Medicine in Houston, Texas are
studying inherited retinal diseases including Lowe's Syndrome.  Families with
at least two affected members and both parents living are needed to
participate in this program.  Other disorders included in the study are
Leber's Congenital Amaurosis, Usher Syndrome (Types I and II), Macular
Degeneration and Polymorphic Macular Degeneration, Lawrence-Moon-Biedl
Syndrome, Rod Monochromacy (Complete Congenital Achromatopsia), Blue Cone
Monochromacy (Congenital Incomplete X-linked Achromatopsia), Choroidermia,
Hereditary X-linked cataracts, and other hereditary diseases with significant
visual impact.

Another important investigation on Lowe's Syndrome is currently underway
at the National Institutes of Child Health and Human Development
(NICHD) Health under the direction of Lawrence Charnas, M.D., NIH/National
Institute of Child Health and Human Development, Bldg. 10, Rm. 8C-429,
Bethesda, MD, 20892, [phone]).

Current research strongly suggests that the Lowe's Syndrome gene controls
production of a specific enzyme, inositol-polyphosphate-5-phosphatase.  This
enzyme discovery will open the door to further investigations into the
metabolic defect and how it relates to various medical problems.

This disease entry is based upon medical information available through
April 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 Lowe's Syndrome, please contact:

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

     Lowe's Syndrome Association
     222 Lincoln Street
     West Lafayette, IN 47806
     [phone]

     NIH/National Institute of Child Health and Human Development (NICHD)
     9000 Rockville Pike
     Bethesda, MD  20892
     [phone]

For Genetic Information and genetic counseling referrals, please contact:

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

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

References

ORAL CARNITINE THERAPY IN CHILDREN WITH CYSTINOSIS AND RENAL FANCONI
SYNDROME.  w. Gahl et al.; J CLIN INVEST (February 1988, issue 81 (2)).  Pp.
549-560.

EFFECT OF THYROCALCITONIN ON RENAL REABSORPTION OF BICARBONATE.
BIOMEDICINE (December 1979, issue 31 (8)).  Pp. 230-233.

THE OCULOCEREBRAL SYNDROME OF LOWE, Charnas, L. and Gahl, W; National
Institutes of Health Institute of Child Health and Human Development,
National Institutes of Health, Bethesda, MD, 1991.

CLINICAL LABORATORY FINDINGS IN THE OCULOCEREBRAL SYNDROME OF LOWE, WITH
SPECIAL REFERENCE TO GROWTH AND RENAL FUNCTION, Charnas, L., et al.; N Eng J
Med, May 9, 1991, (issue 324).  Pp. 1318-1325.