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$Unique_ID{BRK03416}
$Pretitle{}
$Title{Acidemia, Propionic}
$Subject{Acidemia, Propionic Hyperglycinemia with Ketoacidosis and Leukopenia
Ketotic Glycinemia PCC Deficiency Propionyl CoA Carboxylase Deficiency Ketotic
Hyperglycinemia Acidemias, Methylmalonic}
$Volume{}
$Log{}

Copyright (C) 1988, 1989 National Organization for Rare Disorders, Inc.

500:
Acidemia, Propionic

** IMPORTANT **
It is possible the main title of the article (Propionic Acidemia) is not
the name you expected.  Please check the SYNONYMS listing on the next page to
find alternate names, disorder subdivisions, and related disorders covered by
this article.

Synonyms

     Hyperglycinemia with Ketoacidosis and Leukopenia
     Ketotic Glycinemia
     PCC Deficiency
     Propionyl CoA Carboxylase Deficiency

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

     Ketotic Hyperglycinemia
     Acidemias, Methylmalonic

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.


Propionic Acidemia is a very rare genetic form of Ketotic
Hyperglycinemia.  The disorder is due to deficiency of the enzyme propionyl
CoA carboxylase, one of the enzymes necessary in the process of breaking down
amino acids.

Symptoms

Propionic Acidemia has an unpredictable course.  Many of the symptoms
commonly occur later in the course of the disorder and may worsen after
excessive protein intake, gastrointestinal or upper respiratory tract
infections with fever, or constipation.

This disorder is characterized by protein intolerance, acidosis and an
abnormally elevated concentration of ketone bodies (ketosis) in the blood and
body tissues.  Another symptom of Propionic Acidemia is diminished muscle
tone.  A decrease of blood platelets (thrombocytopenia) may also occur.  If
left untreated, the acidosis and ketosis may cause dehydration, lethargy, and
vomiting.  This may lead to coma or seizures which may be life threatening.
Without treatment, brain damage and/or generalized or shocklike (myoclonic)
seizures will occur.  Patients with this disorder may also experience slowed
development, mental retardation.

Liver abnormalities may include fatty infiltration, degeneration, and
swollen liver cells (hepatocytes).  The blood of persons with Propionic
Acidemia contains an increased amount of glycine and a massive amount of
propionate.  An EEG (electroencephalograms) may be abnormal.

Propionic Acidemia patients may also develop symptoms later in infancy.
These tend to be milder than those of the adult form.

Human mother's milk contains less protein than formulas or cow's milk.
Therefore, some researchers suspect that breast feeding may contribute to the
late onset in the milder form of this disorder in some cases.

Causes

Propionic Acidemia is a genetic disorder transmitted through autosomal
recessive genes.  (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.)

Often the parents of patients with this disorder are related
(consanguine).  Symptoms are caused by a deficiency of the enzyme propionyl
CoA carboxylase, which is needed for the metabolism of some of the building
blocks of proteins (amino acids) such as leucine, isoleucine, valine,
threonine, and methionine.  This deficiency results in increased acidity of
the blood.  The mechanism which causes the increased levels of the amino acid
glycine in the blood is not well understood.

Affected Population

Propionic Acidemia is a rare hereditary disorder affecting males and females
in equal numbers.  The form of the disorder which begins later in infancy
occurs even less frequently than the form which is present at birth.

Related Disorders

Symptoms of the following disorders can be similar to those of Propionic
Acidemia.  Comparisons may be useful for a differential diagnosis:

Ketotic Hyperglycinemia is a group of hereditary protein metabolism
disorders.  In each case, a defective enzyme prevents the breakdown of
certain amino acids and lipids.  High levels of the amino acid glycine and
ketones accumulate in the blood and urine.  Clinically, affected infants have
feeding difficulties and developmental, neurological, digestive, and
metabolic problems, as well as increased susceptibility to infections.
Often, complications can be avoided with early treatment.  The disorders are
very rare, with only a few individual cases reported.  Methylmalonic
Acidemias is a form of Ketotic Hyperglycinemia.  (For more information on
this disorder, choose "Ketotic Hyperglycinemia" as your search term in the
Rare Disease Database.)

Methylmalonic Acidemias are one type of organic acidemia.  All known
organic acidemias are inherited as autosomal recessive traits.  They are
caused by an enzyme defect in the breakdown (metabolism of one amino acid.
This results in an abnormally high level of acid in the blood and body
tissues which can cause metabolic acidosis.  Drowsiness, coma, and seizures
are symptoms of metabolic acidosis.  Mental retardation is a long-term
consequence.  The disorders may be caused by either a deficiency of the
enzyme methylmalonyl CoA mutase, methylmalonyl racemase, or of
adenosylcobalamin synthetic enzymes.  Excretion of methylmalonate (a product
of amino acid metabolism) in the urine is abnormally high in people affected
by Methylmalonic Acidemias.  (For more information on this disorder, choose
"Methylmalonic Acidemia" as your search term in the Rare Disease Database.)

Therapies:  Standard

Prenatal diagnosis of Propionic Acidemia is possible by testing the fluid
taken from the fetal sac (amniocentesis) for activity of the enzyme propionyl
coA carboxylase.  However, this method is not very accurate.  An alternate
method of prenatal diagnosis is measuring the levels of abnormal metabolites
such as methyl citrate in the fetal sac fluid.  Diagnosis of the disorder in
suspected patients and/or relatives of patients who may be carriers involves
the measurement of propionic acid in blood or urine, or studies of propionyl-
CoA carboxylase activity in white cell (leukocyte) or connective tissue cell
(fibroblast) extracts.

Treatment for Propionic Acidemia requires fluid and electrolyte therapy.
Sodium bicarbonate is used to decrease the acidity of blood and body tissues
(acidosis).  Or this can be accomplished by either peritoneal dialysis or
exchange transfusions.  However, treatment must begin as soon as possible and
monitoring of blood levels is necessary thereafter.

Long-term treatment involves maintenance of a diet low in protein through
use of special formulas low in the amino acids leucine, isoleucine, valine,
threonine, and methionine.  On these restricted diets patients can experience
good metabolic control with acceptable growth and development if adequate
general nutrition is maintained through use of medical foods.

In carnitine deficiency syndromes, the transport of fatty acids into
mitochondria for oxidation and energy production is impaired.  Because large
amounts of glucose must be used to meet the organism's metabolic
requirements, hypoglycemia often results, and the patient becomes completely
dependent on glucose.

Therapies:  Investigational

Only one patient with Propionic Acidemia has responded to biotin treatment.
A therapeutic trial of this coenzyme of PCC can be performed.

In carnitine deficiency syndromes, the transport of fatty acids into
mitochondria for oxidation and energy production is impaired.  Because large
amounts of glucose must be used to meet the organism's metabolic
requirements, hypoglycemia often results, and the patient becomes completely
dependent on glucose.

This disease entry is based upon medical information available through
December 1989.  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 this disorder, please contact:

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

     Organic Acidemia Association
     522 Lander St.
     Reno, NV  89512
     [phone]

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

     Research Trust for Metabolic Diseases in Children
     53 Beam Street
     Nantwich, Cheshire
     England CW5 5NF
     Telephone:  [phone]

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

For more 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

PROPIONIC ACIDEMIA:  A CLINICAL UPDATE:  Barry Wolf, et al.; Journal of
Pediatrics (December 1981:  issue 99:6).  Pp. 835-846.

METABOLIC BASIS OF INHERITED DISEASE, 5th ed.:  John B. Stanbury, et al.,
eds.; McGraw Hill, 1983.  Pp. 2063-2064.

MENDELIAN INHERITANCE IN MAN, 7th ed.:  Victor A. McKusick; Johns Hopkins
University Press, 1986.  Pp. 1001-1002.

This Report in the Rare Disease Database is based upon outlines prepared
by medical and dental students (1984-1986) at the Medical College of Virginia
for their course in human genetics.