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$Unique_ID{BRK03486}
$Pretitle{}
$Title{Arginase Deficiency}
$Subject{Arginase Deficiency Argininemia Urea Cycle Disorders Inborn Errors of
Urea Synthesis Reye Syndrome}
$Volume{}
$Log{}

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

312:
Arginase Deficiency

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

Synonyms

     Argininemia
     Urea Cycle Disorders
     Inborn Errors of Urea Synthesis

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

     Reye Syndrome

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.


Arginase Deficiency is one of several hereditary urea cycle disorders.
These disorders are caused by a deficiency of one of the enzymes needed for
the incorporation of ammonia into urea, which is normally excreted in the
urine.  These deficiencies cause an excess of ammonia in the blood and body
tissues.  (For more information on the other Urea Cycle Disorders, choose
"urea cycle disorder" as your search term in the Rare Disease Database.)

Symptoms

Arginase Deficiency is characterized in infants by retardation, seizures and
spasticity.  The deficient enzyme is arginase.  If left untreated, the
disorder manifests itself by serious central nervous system disease, but a
life threatening elevation of toxic ammonia in the blood rarely occurs.

Differential diagnosis is based on the presence of an elevated level of
arginine in the blood.

Causes

Arginase Deficiency is an autosomal recessive hereditary disorder in which
the activity of the enzyme arginase is deficient.  This deficiency causes an
accumulation of excess arginine in blood and body tissues.  (Human traits
including the classic genetic diseases, are the product of the interaction of
two genes for that condition, 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 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 show no 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

Arginase Deficiency is a very rare disorder affecting less than a thousand
people in the United States.  Males and females are affected equally.  Onset
of the symptoms occurs at birth, but may not be noticeable for days or weeks
as they progress.

Related Disorders

Reye Syndrome is a combination of acute brain disease (encephalopathy), and
fatty degeneration of the abdominal organs (viscera), which tends to follow
some acute virus infections (such as flu and chickenpox) combined with
certain toxins (usually aspirin).  (For more information, choose "Reye" as
your search term in the Rare Disease Database.)

The following Urea Cycle Disorders can also be found in the Rare Disease
Database.  All are characterized by deficiencies of enzymes that are needed
for different steps in the breakdown of ammonium into urea.  The symptoms of
all Urea Cycle Disorders include hyperammonemia, in different degrees of
severity.  Arginase Deficiency is the mildest form of Urea Cycle Disorder.

N-Acetyl Glutamate Synthetase (NAGS) Deficiency
Ornithine Transcarbamylase (OTC) Deficiency
Carbamyl Phosphate Synthetase (CPS) Deficiency
Citrullinemia
Arginino Succinic Aciduria

Therapies:  Standard

As soon as a urea cycle disorder is suspected, a number of diagnostic tests
should be performed, including measurement of pH to assess the acidity of
blood and body tissues, plasma levels of ammonia, amino acids, and
bicarbonate.  However, before the results of these tests are in, treatment of
hyperammonemia should be started to prevent coma and/or brain damage.

As soon as CPS Deficiency is diagnosed in a newborn baby, dialysis or
exchange transfusion should be started.  If hyperammoniac coma is present
shortly after birth, a combined treatment needs to be started as soon as
possible, which may include hemodialysis.

The orphan drug benzoate/phenylacetate (Ucephan) was approved in 1988 for
use in the prevention and treatment of hyperammonemia in patients with urea
cycle enzymopathy (UCE) due to enzyme deficiencies.  The drug is manufactured
by:

     Kendall McGaw Laboratories, Inc.
     P.O. Box 25080
     Santa Ana, CA  92799-5080

Genetic counseling is imperative for the family of children with CPS
Deficiency.

Therapies:  Investigational

A new investigational drug is being developed by Dr.  Saul Brusilow (see
Resources section of this entry):  sodium (or calcium) phenylbutyrate does not
have an offensive smell.  Like Ucephan it is hoped that this drug may enhance
waste nitrogen excretion and prevent ammonia build up in the blood.

Enzyme replacement therapy shows potential promise for treatment of urea
cycle disorders including CPS Deficiency.  Research on this type of therapy
is in a preliminary stage.  A regimen consisting of acute hemodialysis
followed by a restricted intake of protein, plus sodium benzoate, sodium
phenylacetate, and arginine or citrulline is being used on an experimental
basis.

Clinical trials are underway to study L-Carnitine in amino acid and fat
metabolism.  Interested persons may wish to contact:

     Charles R. Roe, M.D.
     Box 3028
     Duke University Medical Center
     Durham, NC  27710
     [phone]

to see if further patients are needed for this research.

This disease entry is based upon medical information available through
January 1992.  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 Arginase Deficiency, please contact:

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

     National Urea Cycle Disorders Foundation
     4559 Vauxhall Rd.
     Richmond, VA  23234-3556

     Saul Brusilow, M.D.
     Professor of Pediatrics
     Johns Hopkins Hospital
     600 N. Wolfe St.
     Baltimore, MD 21205
     [phone]

     Steve Cederbaum, MD
     Professor of Pediatrics
     UCLA Medical School
     Los Angeles, CA  90024

     National Digestive Diseases Information Clearinghouse
     Box NDDIC
     Bethesda, MD  20892
     [phone]

     Research Trust for Metabolic Diseases in Children
     Golden Gates Lodge, Weston Rd.
     Crewe CW1 1XN, England
     Telephone:  [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

DISORDERS OF THE UREA CYCLE:  Saul W. Brusilow; Hospital Practice (October
15, 1985:  issue 305).  Pp. 65-72.

SYMPTOMATIC INBORN ERRORS OF METABOLISM IN THE NEONATE:  Saul W. Brusilow
and David L. Vallee;  In:  Current Therapy in Neonatal-Perinatal Medicine.
Marcel Decker, 1985.  Pp. 207-212.