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$Unique_ID{BRK03776}
$Pretitle{}
$Title{Glutaricaciduria II}
$Subject{Glutaricaciduria II Ethylmalonic Adipicaciduria GA II Glutaric
Acidemia II Glutaric Aciduria II Glutaricacidemia II Glutaricaciduria Type IIA
GA IIA Multiple Acyl-CoA Dehydrogenase Deficiency Glutaricaciduria IIB
Ethylmalonic Adipicaciduria GA IIB Glutaricaciduria I Medium Chain CoA
Dehydrogenase Deficiency MCAD}
$Volume{}
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Copyright (C) 1987, 1988, 1990, 1992 National Organization for Rare
Disorders, Inc.

378:
Glutaricaciduria II

** IMPORTANT **
It is possible the main title of the article (Glutaricaciduria II) 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

     Ethylmalonic Adipicaciduria
     GA II
     Glutaric Acidemia II
     Glutaric Aciduria II
     Glutaricacidemia II

Disorder Subdivisions:

     Glutaricaciduria Type IIA, also known as GA IIA, Multiple Acyl-CoA
     Dehydrogenase Deficiency
     Glutaricaciduria IIB, also known as Ethylmalonic Adipicaciduria, GA IIB

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

     Glutaricaciduria I
     Medium Chain CoA Dehydrogenase Deficiency (MCAD)

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.

There are two forms of Glutaricaciduria II which occur during different
stages of life.  They are both forms of organic acidemias which are a group
of metabolic disorders characterized by excess acid in the blood and urine.

1) Glutaricaciduria IIA (GA IIA), Neonatal Form of Glutaricaciduria II.
This neonatal form of Glutaricaciduria II is a very rare, sex-linked
hereditary disorder 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.

2) Glutaricaciduria IIB (GA IIB; Ethylmalonic Adipicaciduria), Adult Form
of Glutaricaciduria II.

This milder form of the disorder is inherited as an autosomal recessive
trait.  Acidity of the body tissues (metabolic acidosis), and a low blood
sugar level (hypoglycemia) without an elevated level of ketones in body
tissues (ketosis), occur during adulthood.  Large amounts of glutaric acid in
the blood and urine are caused by a deficiency of the enzyme "multiple acyl-
CoA dehydrogenase".

Symptoms

1) Glutaricaciduria IIA is the neonatal form of the disorder, and is the more
serious type.  This form is characterized by episodes of vomiting and a
severely depressed blood sugar level (hypoglycemia).  An increased level of
ammonia in the blood (hyperammonemia) also occurs.  Glutaric, lactic,
butyric, isobutyric, 2-methylbutyric, ethylmalonic, adipic, and isovaleric
acids (all organic acids) are produced during metabolism of amino acids.
These acids are excreted through the urine in dangerously high amounts in
persons with Glutaricaciduria.

2) Glutaricaciduria IIB is the adult form of the disorder.  This
extremely rare form of Glutaricaciduria has been identified in a few adults
whose symptoms were vomiting, severe hypoglycemia, and fatty infiltration of
the liver.  One sibling of a woman with Glutaricaciduria IIB had only nausea,
and a 'stale' odor to her breath; she suffered a hypoglycemic coma.  Another
sibling of this patient had liver disease including jaundice, liver
enlargement (hepatomegaly), and hypoglycemia.  Excessive amounts of glutaric
and ethylmalonic acid were found in the urine of all 3 relatives.

Causes

The neonatal form of Glutaricaciduria II GA IIA) is caused by deficiency of
an element common to all three acyl CoA dehydrogenase enzymes, so that the
disorder may also be called Multiple Acyl CoA Dehydrogenase Deficiency.  This
deficiency causes an excess of several organic acids, especially glutaric
acid, in the urine.  This type of Glutaricaciduria is inherited through
autosomal recessive genes.

The adult form of Glutaricaciduria II (GA IIB) is also caused by
deficiencies of acyl-CoA dehydrogenase.  However, the mode of inheritance in
this form of this disorder is autosomal recessive.  The deficiencies cause
an excess of glutaric and ethylmalonic acids in the urine.

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

GA IIA affects males only, with onset of symptoms at birth.  GA IIB affects
males and females equally.  Symptoms of this form of the disorder first
appear during adult life.  The neonatal and the adult form of the disorder
combined affect less than 200 persons in the United States.

Related Disorders

Glutaricaciduria I is a rare hereditary metabolic disorder caused by a
deficiency of the enzyme glutaryl-CoA dehydrogenase.  The disorder is
characterized by decreased muscle tone (hypotonia), vomiting, and acidity of
the blood.  The patient may have involuntary movements of the trunk and limbs
(dystonia or athetosis) and mental retardation may also occur.  (For more
information on this disorder, choose "Glutaricaciduria I" as your search term
in the Rare Disease Database.)

Medium Chain CoA Dehydrogenase Deficiency (MCAD) is a very rare metabolic
disorder characterized by a deficiency of the enzyme CoA dehydrogenase.  This
enzyme is needed in the breakdown (metabolism) of fats.  Low blood sugar
(hypoglycemia), lack of energy (lethargy) and possibly coma, associated with
fatty changes in the liver, usually occur.  During hypoglycemic periods,
tests usually show massive amounts of dicarboxylic acid in the urine.

There are many rare disorders caused by enzyme deficiencies.  To locate
these disorders on the Rare Disease Database, choose "Enzyme Deficiency" as
your search term.

Therapies:  Standard

Glutaricaciduria is diagnosed when excessive glutaric acid is found in the
urine or by enzyme assay in white blood cells (leukocytes).  Detection of the
disorder in a fetus may be possible by testing for the enzyme acyl-CoA
dehydrogenase.  It is imperative to test for this disorder as soon after
birth as possible.  Peritoneal dialysis or hemodialysis may be necessary.
The usefulness of restricting the amino acids lysine, hydroxylysine, and
tryptophan (which generate glutaric acid), is not established at the present
time.  Acute episodes of acidity in blood and body tissues (acidosis) and
dehydration are treated with fluids and bicarbonate.  Many of the adverse
effects or organic acidemias are due to secondary carnitine depletion.  Such
patients should have plasma carnitine measured and, if deficient, begin a
supplement of 100-300 mg/kg/day of oral l-carnitine.

Genetic counseling is recommended for families of children with
Glutaricaciduria.

Therapies:  Investigational

Clinical trials are underway to study stable isotope technique in
glucogenesis and Krebs cycle and patient response to treatment.  Interested
persons may wish to contact:

     Dr. W.N. Paul Lee
     Harbor University of CA, Los Angeles Medical Center
     Dept. of Pediatrics, Box-16
     1000 W. Carson St.
     Torrance, CA  90509
     [phone]

to see if further patients are needed for this research.

This disease entry is based upon medical information available through
January 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 Glutaricaciduria, please contact:

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

     Lactic Acidosis Support Group
     P.O. Box 480282
     Denver, CO  80248
     [phone]

     National Urea Cycle Disorders Foundation
     4559 Vauxhall Rd.
     Richmond, VA  23234-3556

     Saul Brusilow, M.D.
     301 Children's Medical and Surgical Center
     Johns Hopkins Hospital
     600 N. Wolfe St.
     Baltimore, MD  21205
     [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
     Golden Gates Lodge, Weston Rd.
     Crewe CW1 1XN, England
     Telephone:  [phone]

For more information on genetics and genetic counseling referrals, please
contact:

     March of Dimes Birth Defects Foundation
     1274 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

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. 24-27.

MENDELIAN INHERITANCE IN MAN, 6th ed:  Victor A. McKusick; Johns Hopkins
University Press, 1983.  Pp. 703, 735, 1038.