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$Unique_ID{BRK03414}
$Pretitle{}
$Title{Acidemia, Isovaleric}
$Subject{Acidemia, Isovaleric Isovaleric Acidaemia Isovalericacidemia
Isovaleric Acid CoA Dehydrogenase Deficiency Isovaleryl CoA Carboxylase
Deficiency IVA Acidemias, Methylmalonic Glutaricaciduria II Maple Syrup Urine
Disease Non-Ketotic Hyperglycinemia (Glycinemia) Propionic Acidemias}
$Volume{}
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Copyright (C) 1988, 1989 National Organization for Rare Disorders, Inc.

504:
Acidemia, Isovaleric

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

Synonyms

     Isovaleric Acidaemia
     Isovalericacidemia
     Isovaleric Acid CoA Dehydrogenase Deficiency
     Isovaleryl CoA Carboxylase Deficiency
     IVA

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

     Acidemias, Methylmalonic
     Glutaricaciduria II
     Maple Syrup Urine Disease
     Non-Ketotic Hyperglycinemia (Glycinemia)
     Propionic Acidemias

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.

Isovaleric Acidemia is a hereditary metabolic disorder.  It is
characterized by a deficiency of the enzyme isovaleryl CoA dehydrogenase.
The disorder occurs in both an acute and a chronic intermittent form.  In
the acute form of Isovaleric Acidemia, vomiting, refusal to eat, and
listlessness usually occur.  With treatment and low protein diet, the
disorder becomes chronically intermittent, and a nearly normal life is
possible.

Symptoms

Isovaleric Acidemia is a rare metabolic disorder that occurs in an acute and
a chronic intermittent form.  The disorder may start as early as 2 weeks of
age or as late as 1 year.  It is characterized by attacks of vomiting, lack
of appetite and listlessness.  Infants with Isovaleric Acidemia become
increasingly listless and they sometimes shake or tremble.  They often have a
lower than normal body temperature (hypothermia).  In most cases a strong
odor like that of "sweaty feet" occurs.  Intermittent episodes are usually
triggered by upper respiratory infections or excessive eating of high protein
foods.   Severe acidity and the presence of ketone bodies in blood and body
tissues (ketoacidosis) usually follows and patients may lapse into a coma.

Ketoacidotic episodes tend to occur frequently in early infancy and young
childhood, but their frequency usually diminishes as the patient grows older.
Children with Isovaleric Acidemia often show a natural aversion to protein
foods, even at a young age.

Causes

Isovaleric Acidemia is a genetic disorder inherited through autosomal
recessive genes.  Symptoms are the result of a deficiency of the enzyme
isovaleric co-enzyme A (CoA) dehydrogenase, which is needed for the breakdown
of the amino acid leucine.  (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

Isovaleric Acidemia is a rare disorder affecting males and females in equal
numbers, usually beginning during infancy.

Related Disorders

Methylmalonic Acidemias are a group of organic acidemias.  All known organic
acidemias are inherited as autosomal recessive traits.  Each is caused by an
enzymatic defect in the metabolism of one amino acid.  Without treatment,
this may result in an abnormally high level of acid in the blood and body
tissues (acidosis).  In acute cases, drowsiness, coma, seizures and mental
retardation may occur.  Methylmalonic Acidemias may be caused either by 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.  (For more
information, choose Methylmalonic Acidemia" as your search term in the Rare
Disease Database.)

Glutaricaciduria II (Glutaric Acidemia II) occurs in two forms during two
different stages of life.  Both forms are organic acidemias, a group of
metabolic disorders characterized by the presence of excess acid in the blood
and urine.

Glutaricaciduria IIA (Glutaric Acidemia IIA), the neonatal onset form of
Glutaricaciduria, is a very rare, sex-linked hereditary disorder.  It is
characterized by large amounts of glutaric and other acids in blood and
urine.  Some researchers believe the disorder is caused by a defect in the
breakdown of acyl-CoA compounds.

Glutaricaciduria IIB (Glutaric Acidemia IIB;  Ethylmalonic
Adipicaciduria), the milder adult onset form of the disorder, is inherited as
an autosomal recessive trait.  Symptoms may include acidity of the body
tissues (acidosis), and a low blood sugar level (hypoglycemia) without an
elevated level of ketones in body tissues (ketosis).  Large amounts of
glutaric acid in the blood and urine are caused by a deficiency of the enzyme
"multiple acyl-CoA dehydrogenase"  (For more information on this disorder,
choose "Glutaricaciduria II" sd your search term in the Rare Disease
Database").

Maple Syrup Urine Disease is a hereditary disorder resulting from
abnormal metabolism of the four "branched chain" amino acids (protein
building blocks), leucine, isoleucine, valine, and alloisoleucine.  Without
treatment, spasticity alternating with poor muscle tone, convulsions, and
coma characterize the disorder.  It derives its name from the odor of the
patients' urine and sweat.  (For more information on this disorder, choose
"Maple Syrup Urine" as your search term in the Rare Disease Database.)

Non-Ketotic Hyperglycinemia is a genetic disorder characterized as an
inborn error of amino acid metabolism.  Large amounts of the amino acid
glycine tend to accumulate in body fluids, particularly in the cerebrospinal
fluid.  After severe illness beginning soon after birth, most patients become
severely mentally retarded and may develop seizures.  (For more information
on this disorder, choose "Non-Ketotic Hyperglycinemia" as your search term in
the Rare Disease Database.)

Propionic Acidemia is a very rare genetic form of Ketotic
Hyperglycinemia.  The disorder is characterized by a deficiency of the
coenzyme propionyl CoA carboxylase, one of the enzymes necessary in the
process of breaking down amino acids.  Propionic Acidemia occurs in two
forms.  One form begins at birth and the other is milder, occurring less
frequently, with symptoms starting during later infancy.  Without treatment,
dehydration, drowsiness, lethargy, vomiting, and in some cases coma may
develop.  (For more information on thisa disorder, choose "Propionic
Acidemia" as your search term in the Rare Disease Database.)

Therapies:  Standard

Isovaleric Acidemia can be diagnosed prenatally by measuring the amounts of
isovalerylglycine in amniotic fluid and urine.  The disorder is treated by a
diet with moderate restriction of the amino acid leucine and supplementation
of L-carnitine.  Other treatment is symptomatic and supportive.  Genetic
counseling is recommended for families of children with Isovaleric Acidemia.
Administration of glycine at 150-300 mg/day is life-saving and may permit
normal growth and development.

Therapies:  Investigational

This disease entry is based upon medical information available through
December 1988.  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 Isovaleric Acidemia, 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

     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:

     Alliance of Genetic Support Groups
     35 Wisconsin Circle, Suite 440
     Chevy Chase, MD  20815
     (800) 336-GENE
     [phone]

     March of Dimes Birth Defects Foundation
     1275 Mamaroneck Avenue
     White Plains, NY  10605
     [phone]

References

THE METABOLIC BASIS OF INHERITED DISEASE, 5th ed.:  John B. Stanbury, et
al., eds.;  McGraw Hill, 1983.  Pp. 457-461.

THE RESPONSE TO L-CARNITINE AND GLYCINE THERAPY IN ISOVALERIC ACIDAEMIA:  C.
de Sousa, et al.;  European Journal Pediatr (February 1986:  issue 144(5)).
Pp. 451-456.

STABLE ISOTOPE DILUTION ANALYSIS OF ISOVALERYLGLYCINE IN AMNIOTIC FLUID
AND URINE AND ITS APPLICATION FOR THE PRENATAL DIAGNOSIS OF ISOVALERIC
ACIDEMIA:  D.G. Hine, et al.;  Pediatr Res (March 1986:  issue 20(3)).  Pp.
222-226.