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$Unique_ID{BRK04068}
$Pretitle{}
$Title{Ornithine Transcarbamylase Deficiency}
$Subject{Ornithine Transcarbamylase Deficiency Hyperammonemia Type II OTC
Deficiency Ornithine Carbamyl Transferase Deficiency Ornithine Carbamyl
Transferase Deficiency Urea Cycle Disorder OTC Type UCE Urea Cycle Enzyme
Disorders Citrullinemia Argininosuccinic Aciduria Arginase Deficiency N-Acetyl
Glutamate Synthetase Deficiency Carbamyl Phosphate Synthetase Deficiency Reye
Syndrome Organic Acidemia}
$Volume{}
$Log{}

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

309:
Ornithine Transcarbamylase Deficiency

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

Synonyms

     Hyperammonemia Type II
     OTC Deficiency
     Ornithine Carbamyl Transferase Deficiency
     Ornithine Carbamyl Transferase Deficiency
     Urea Cycle Disorder, OTC Type
     UCE

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

     Urea Cycle Enzyme Disorders, including:
     Citrullinemia,
     Argininosuccinic Aciduria,
     Arginase Deficiency,
     N-Acetyl Glutamate,
     Synthetase Deficiency,
     Carbamyl Phosphate Synthetase Deficiency,
     Reye Syndrome
     Organic Acidemia

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.


Ornithine Transcarbamylase Deficiency is a rare inborn error of
metabolism and one of six inherited disorders of the urea cycle.  The urea
cycle is a series of chemical reactions in the liver that break down ammonia
into urea.  Ammonia is toxic to the body.  Urea cycle disorders are caused by
deficiencies of certain proteins (enzymes) that act to break down the ammonia
into urea which is then eliminated from the body.  These enzyme deficiencies
cause an abnormal accumulation of ammonia in the blood and body tissues.

Symptoms

Ornithine Transcarbamylase Deficiency is a rare metabolic disorder
characterized by excessive levels of ammonia (hyperammonemia) in the blood
and body tissues.  Symptoms of this disorder may include lack of appetite,
vomiting, drowsiness, seizures, and/or coma.  The liver may be abnormally
enlarged (hepatomegaly).

The diagnosis of Ornithine Transcarbamylase Deficiency is confirmed by a
laboratory test that detects an abnormally high level of orotate in the
urine.  This test distinguishes Ornithine Transcarbamylase Deficiency from
other urea cycle enzyme disorders.  Citrulline is also absent in the blood.
(For more information about Urea Cycles Disorders, see the Related Disorders
Section of this report.)

Immediate treatment after the diagnosis of Ornithine Transcarbamylase
Deficiency is imperative.  If left untreated this disorder can be
life-threatening and can result in brain damage and coma.

Causes

Ornithine Transcarbamylase Deficiency is inherited as an X-linked genetic
trait.  The symptoms of Ornithine Transcarbamylase Deficiency develop due to
the 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, 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.

Males who have only one of a pair of genes that result in Ornithine
Transcarbamylase Deficiency (hemizygotes) have extreme symptoms, whereas
females who have two different genes of a pair (heterozygotes) for this
disorder have milder symptoms.  Approximately one-third of the cases may be
due to a new mutation (de novo) in the gene responsible for Ornithine
Transcarbamylase Deficiency.

Affected Population

Ornithine Transcarbamylase Deficiency is a very rare disorder that affects
less than 1000 people in the United States.  This disorder occurs in
approximately 1 in 25,000 births.  In males, symptoms typically begin during
the first few days of life.  Females who carry the defective gene may have
symptoms that are mild, or have no symptoms at all.  Some women who are
carriers of the gene for Ornithine Transcarbamylase Deficiency may not
experience abnormally high levels of ammonia (hyperammonemia) until pregnancy
or delivery.

Related Disorders

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

Urea Cycle Enzyme Deficiencies (UCE) are a group of rare inherited
metabolic disorders.  The six disorders of the urea cycle are Citrullinemia,
Argininosuccinic Aciduria, Arginase Deficiency, N-Acetyl Glutamate Synthetase
Deficiency, Carbamyl Phosphate Synthetase Deficiency, and Ornithine
Transcarbamylase Deficiency.  The symptoms of all urea cycle disorders vary
in severity and result from the excessive accumulation of ammonia in the
blood and body tissues (hyperammonemia).  Symptoms include lack of appetite,
vomiting, drowsiness, seizures, and/or coma.  The liver may be abnormally
enlarged (hepatomegaly).  (For more information choose "Citrullinemia,"
"Argininosuccinic Aciduria," "Arginase Deficiency," "N-Acetyl Glutamate
Synthetase Deficiency," and "Carbamyl Phosphate Synthetase Deficiency" as
your search terms in the Rare Disease Database.)

Reye Syndrome is a rare childhood disease characterized by liver failure,
abnormal brain function (encephalopathy), abnormally low levels of glucose
(hypoglycemia), and high levels of ammonia in the blood.  This disorder
usually follows a viral infection.  It may be triggered by the use of aspirin
in children recovering from chicken pox or influenza.  Deficiencies of the
urea cycle enzymes are thought to play a role in the development of Reye
Syndrome.  Symptoms include vomiting, diarrhea, rapid breathing,
irritability, fatigue, and behavioral changes.  Neurological symptoms may be
life-threatening and include seizures, stupor, and coma.  (For more
information on this disorder, choose "Reye" as your search term in the Rare
Disease Database.)

Organic Acidemias are a group of rare inherited metabolic disorders
characterized by the excessive accumulation of various acids in the blood.
Symptoms may include constipation, muscle weakness and low levels of
platelets in the blood (thrombocytopenia).  People with these disorders also
have hyperammonemia and experience symptoms that are similar to those of urea
cycle enzyme disorders.  (For more information, choose "Acidemia" as your
search term in the Rare Disease Database.)

Therapies:  Standard

When a person is suspected of having Ornithine Transcarbamylase Deficiency or
any other urea cycle disorder, a number of diagnostic tests should be
performed.  These include measurement of pH of the blood and body tissues to
determine if the blood is acidic, the levels of ammonia, amino acids and
bicarbonate in the blood, urinary organic acids, and blood gases.  Before the
results of these tests are in, treatment of hyperammonemia should be started
to prevent coma and/or brain damage.

As soon as Ornithine Transcarbamylase Deficiency is diagnosed in a male
newborn, a procedure that removes the excess ammonia from the blood
(hemodialysis) or blood exchange transfusions should be started immediately.
If coma is present shortly after birth due to abnormally high levels of
ammonia, then a combined treatment needs to be started as soon as possible,
which may include hemodialysis.

If the carrier status for the Ornithine Transcarbamylase Deficiency gene
is known, a test (linkage analysis) can be given that can detect urea cycle
enzyme defects in the developing fetus.  Also, women who are at risk for
these deficiencies may be tested for the presence of the defective gene.

The orphan drug benzoate/phenylacetate (Ucephan) has been approved 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 people with Ornithine
Transcarbamylase Deficiency and their families.

Therapies:  Investigational

The orphan drug sodium (or calcium) phenylbutyrate is being developed for use
in the treatment of hyperammonemia, including those people with Ornithine
Transcarbamylase Deficiency.  This drug has the advantage of not having the
offensive odor that is associated with benzoate/phenylacetate.  For more
information, patients should have their physicians contact:

     Dr. Saul Brusilow
     Professor of Pediatrics
     301 Children's Medical and Surgical Center
     John Hopkins Hospital
     600 North Wolfe Street
     Baltimore, MD 21205
     [phone]

Clinical trials are underway to study the orphan drug L-Carnitine in
amino acid and fat metabolism as it relates to urea cycle disorders,
including Ornithine Transcarbamylase Deficiency.  For more information, have
your physician contact:

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

or

     A. Kimberly Iafolla, M.D.
     Duke University Medical Center
     Durham, NC 27710
     [phone]

In people with Ornithine Transcarbamylase Deficiency that does not
respond to drug therapy, liver transplantation may be considered in some
cases.  More study is needed to determine the long-term safety and
effectiveness of this procedure for the most severe cases of Ornithine
Transcarbamylase Deficiency.

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 Ornithine Transcarbamylase 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

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

     Saul Brusilow, M.D., Professor of Pediatrics
     301 Children's Medical and Surgical Center
     Johns Hopkins Hospital
     600 North Wolfe Street
     Baltimore, MD  21205
     [phone]

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

     British Organic Acidemia Association
     5 Saxon Rd.
     Ashford, Middlesex TW15 1QL
     England

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

For Genetic Information and Genetic Counseling Referrals:

     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

MENDELIAN INHERITANCE IN MAN, 10th Ed.:  Victor A. McKusick, Editor:  Johns
Hopkins University Press, 1992.  Pp. 1937-1942.

THE METABOLIC BASIS OF INHERITED DISEASE, 6th Ed.:  Charles R. Scriver, et
al., Editors; McGraw Hill, 1989.  Pp. 635-37, 645-46.

CECIL TEXTBOOK OF MEDICINE, 19th Ed.:  James B. Wyngaarden, and Lloyd H.
Smith, Jr., Editors; W.B. Saunders Co., 1990.  Pp. 1105, 1118.

BIRTH DEFECTS ENCYCLOPEDIA, Mary Louise Buyse, M.D., Editor-In-Chief;
Blackwell Scientific Publications, 1990.  Pp. 1307-1308.

PRINCIPLES OF NEUROLOGY, 4th Ed.; Raymond D. Adams, M.D. and Maurice
Victor, M.D., Editors; McGraw-Hill Information Services Company, 1989.  Pp.
779.

DISORDERS OR 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.

PROSPECTIVE TREATMENT OF UREA CYCLE DISORDERS. N.E. Maestri; J Pediatr
(Dec 1991; 119(6)).  Pp. 923-28.

ALLOPURINOL CHALLENGE TEST IN CHILDREN. A.B. Burlina; J Inherit Metab Dis
(1992; 15(5)).  Pp. 707-712.

A CASE STUDY:  UREA CYCLE DISORDER.  M.M. Gallagher; Neonatal Netw (Sept
1991; 10(2)).  Pp. 35-44.