CD-ROM Today 1996 January/CD-ROM Today 1996 January.iso/dp/0416/04160.txt

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$Unique_ID{BRK04160}
$Pretitle{}
$Title{Pyruvate Carboxylase Deficiency}
$Subject{Pyruvate Carboxylase Deficiency PC Deficiency Group A PC Deficiency
Group B PC Deficiency Leigh's Disease Pyruvate Decarboxylase Deficiency
Wernicke-Korsakoff Syndrome}
$Volume{}
$Log{}

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

873:
Pyruvate Carboxylase Deficiency

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

Synonyms

     PC Deficiency

Disorder Subdivisions:

     Group A PC Deficiency
     Group B PC Deficiency

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

     Leigh's Disease
     Pyruvate Decarboxylase Deficiency
     Wernicke-Korsakoff 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.

Pyruvate Carboxylase Deficiency is a rare genetic metabolic disorder that
is present at birth.  It is classified as a lactic acidemia because the
conversion of pyruvate to oxaloacetate is blocked, impairing a
gluconeogenesis and resulting in an overabundance of lactic acid in the
blood.

Major symptoms may include brain metabolism degeneration, delayed
development, seizures, muscle weakness (hypotonia) and acidosis.

Symptoms

Pyruvate Carboxylase Deficiency symptoms include:  failure to thrive, lack of
motor development, seizures, vomiting, stiffened muscles (spasticity) and
unusual eye motion.

Causes

Pyruvate Carboxylase Deficiency is inherited through autosomal recessive
traits.  The gene responsible for the disease is located on the long arm of
chromosome 11.  (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 from 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

Pyruvate Carboxylase Deficiency is a very rare metabolic disorder that
affects males and females in equal numbers.

Related Disorders

Symptoms of the following disorders can be similar to those of Pyruvate
Carboxylase Deficiency.  Comparisons may be useful for a differential
diagnosis.

Leigh's Disease is a genetic metabolic disorder characterized by lesions
of the brain, spinal cord, optic nerve and in some cases, an enlarged heart.
The disorder is usually first diagnosed during infancy but may begin later.
Symptoms during infancy may include low body weight, slow growth, tremors,
skin changes and interrupted breathing patterns.  Progressive neurological
disturbances, mental retardation, slurred speech and loss of motor
coordination (ataxia) may occur in cases that begin during or after infancy.
Abnormalities of eye movements and other vision problems may develop in cases
with later onset.  For more information on this disorder, choose "Leigh" as
your search term in the Rare Disease Database.

The presentation of Pyruvate Dehydrogenase Complex Deficiency may range
from severe acidosis appearing during the first few days of life to recurrent
episodes of muscle incoordination (ataxia) often associated with upper
respiratory infection or other minor stress.  The growth rate may be slowed
in some children with this disorder.  Varying degrees of neurologic deficits
and mental retardation may occur in patients with this type of acidosis.
Severe acidosis due to abnormally high levels of lactic acid usually appear
shortly after birth.  Lower levels may follow a meal high in carbohydrates.
For more information on this disorder, choose "Pyruvate Dehydrogenase" as
your search term in the Rare Disease Database.

Wernicke-Korsakoff Syndrome is also known as Cerebral Beriberi.  It is
characterized by psychotic symptoms known as Korsakoff's psychosis and by
degeneration of other brain functions known as Wernicke's encephalopathy.  In
Korsakoff's psychosis there is mental confusion.  Other encephalopathic
symptoms include involuntary, rapid eye movements, paralysis of the eye
muscles, coma and death if untreated.  For more information on this disorder,
choose "Korsakoff" as your search term in the Rare Disease Database.

Therapies:  Standard

Treatment of Pyruvate Carboxylase Deficiency consists of dietary limitation
of protein and carbohydrate.  Since this disorder requires biotin or a
cofactor, some cases may respond to pharmacologic doses of biotin.

Genetic counseling will be of benefit for families.  Other treatment is
symptomatic and supportive.

Therapies:  Investigational

Treatment of severe lactic acidosis with Dichloroacetate appears to improve
certain laboratory tests, but does not result in improvement of symptoms.  A
study published in the November 26, 1992 New England Journal of Medicine
indicated that only twelve percent of the Dichloroacetate-treated patients
survived and seventeen percent of the placebo-treated group survived.
Scientists do not understand why this appears to reduce arterial-blood
lactate concentrations and pH, but fails to alter the disease.

The National Institutes of Health (NIH) is sponsoring the Human Genome
Project which is aimed at mapping every gene in the human body and learning
why they sometimes malfunction.  It is hoped that this new knowledge will
lead to prevention and treatment of birth defects in the future.

This disease entry is based upon medical information available through
December 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 Pyruvate Carboxylase Deficiency, please contact:

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

     Lactic Acidosis Support Group
     1620 Marle Ave.
     Denver, CO  80229
     [phone]

     Dr. Peter Stacpoole
     College of Medicine
     University of Florida
     Box J-226, JHMHC
     Gainesville, FL 32610

     Dr. Saul Brusilow
     The Johns Hopkins Hospital
     301 Children's Medical & Surgical Center
     600 North Wolfe St.
     Baltimore, MD 21205
     [phone]

     NIH/National Institute of Neurological Disorders & Stroke (NINDS)
     9000 Rockville Pike
     Bethesda, MD  20892
     [phone]
     [phone]

     Children's Brain Diseases Foundation for Research
     350 Parnassus, Suite 900
     San Francisco, CA 94117
     [phone]
     [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:

     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, 9th Ed.:  Victor A. McKusick, Editor:  Johns
Hopkins University Press, 1990.  Pp. 1451.

THE METABOLIC BASIS OF INHERITED DISEASE, 6th Ed.:  Charles R. Scriver, et
al., Editors; McGraw Hill, 1989.  Pp. 872-878.

BIRTH DEFECTS ENCYCLOPEDIA, Mary Louise Buyse, M.D., Editor-In-Chief;
Blackwell Scientific Publications, 1990.  Pp. 1449-1450.

PYRUVATE CARBOXYLASE DEFICIENCY:  ACUTE EXACERBATION AFTER ACTH TREATMENT
OF INFANTIL SPASMS., Rutledge, S.L. et al.; Pediatr Neurol, July-August,
1989, (issue 5 (4)).  Pp. 249-252.

DETERMINATION OF U-13C GLUCOSE TURNOVER INTO VARIOUS METABOLITE POOLS FOR
THE DIFFERENTIAL DIAGNOSIS OF LACTIC ACIDEMIAS., Kassel, DB, et al.; Anal
Biochem, February 1, 1989, (issue 176 (2)).  Pp. 382-389.

CONTROLLED CLINICAL TRIAL OF DICHLOROACETATE FOR TREATMENT OF LACTIC
ACIDOSIS IN ADULTS:  P.W. Stacpoole, et al.; The New England Journal of
Medicine; (November 26, 1992, issue 327 (22)).  Pp. 1564-69.