CD-ROM Today 1996 January/CD-ROM Today 1996 January.iso/dp/0348/03487.txt

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$Unique_ID{BRK03487}
$Pretitle{}
$Title{Arginino Succinic Aciduria}
$Subject{Arginino Succinic Aciduria AL Deficiency Arginino Succinase
Deficiency ASA Deficiency Urea Cycle Disorders Inborn Errors of Urea
Synthesis}
$Volume{}
$Log{}

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

311:
Arginino Succinic Aciduria

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

Synonyms

     AL Deficiency
     Arginino Succinase Deficiency
     ASA Deficiency
     Urea Cycle Disorders
     Inborn Errors of Urea Synthesis

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.


Arginino Succinic Aciduria is one of several hereditary urea cycle
disorders.  These disorders are caused by a deficiency of one of the enzymes
needed for the breakdown of ammonia into urea, which is normally excreted in
the urine.  The deficiencies cause an excess of ammonia in the blood and body
tissues.  (For more information, choose "Urea Cycle Disorder" as your search
term in the Rare Disease Database.)

In Arginino Succinic Aciduria the deficient enzyme is argininosuccinase.
If left untreated, the disorder manifests itself by an elevated level of
toxic ammonia in the blood (hyperammonemia).  This imbalance may lead to
brain damage and eventually to coma.

Symptoms

Arginino Succinic Aciduria is characterized in infants by an excess of
ammonia in the blood (hyperammonemia).  This condition usually causes
lethargy, lack of appetite, vomiting, seizures and coma.  The blood plasma
level of citrulline is moderately elevated.  The plasma level of arginino-
succinic acid is markedly increased, too.  Differential diagnosis is based on
the presence of the elevated level of the latter.

Immediate treatment after diagnosis in newborn babies is imperative.  If
left untreated, brain damage, coma and death will occur.

Causes

Arginino Succinic Aciduria is an autosomal recessive hereditary disorder in
which the activity of the enzyme arginino succinase is deficient.  This
deficiency causes an accumulation of excess ammonia 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

Arginino Succinic Aciduria 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 usually occur at birth, but may not be
noticeable for days or weeks.

Related Disorders

Organic Acidemias are characterized by hyperammonemia associated with
metabolic acidosis, with an anion gap, and sometimes ketonuria.  These
disorders are also of genetic origin and affect the Urea Cycle as a secondary
phenomenon.

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.  They are all characterized by deficiencies of enzymes that are
needed for different steps in the incorporation of ammonium into urea.  The
symptoms of all Urea Cycle Disorders result from hyperammonemia, in different
degrees of severity.

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

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.

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

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 orginine or citrulline is being used on an experimental
basis.

Two new investigational drugs, sodium (or calcium) benzoate, and sodium
(or calcium) phenylacetate, are used to enhance waste nitrogen excretion.
Thus they prevent toxic ammonia buildup in the blood.  These orphan drugs
have been developed by Dr. Saul Brusilow (see Resources section of this
entry) who is also developing sodium (or calcium) phenylbutyrate which does
not have an offensive smell.

The 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

For information on additional therapies that have been designated as
Orphan Drugs in the last few months, please return to the main menu of NORD
Services and access the Orphan Drug Database.

Therapies:  Investigational

This disease entry is based upon medical information available through
February 1990.  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 Citrullinemia, 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

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

     Saul Brusilow, M.D.
     301 Children's Medical and Surgical Center
     Johns Hopkins Hospital
     600 N. Wolfe St.
     Baltimore, MD  21205
     [phone]

     The National Kidney Foundation
     30 East 33rd St.
     New York, NY  10016
     [phone]
     [phone]

     American Kidney Fund
     6110 Executive Blvd., Suite 1010
     [phone]
     [phone]
     [phone] (MD)

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

For information on genetics 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.