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$Title{Glutaricaciduria I}
$Subject{Glutaricaciduria I GA I Glutaric Acidemia I Glutaric Aciduria I
Glutaricacidemia I Glutaryl-CoA Dehydrogenase Deficiency Dicarboxylic
Aminoaciduria Glutaurate-Aspartate Transport Defect Glutaricaciduria IIA GA
IIA Glutaricaciduria IIB GA IIB}
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Copyright (C) 1987, 1990 National Organization for Rare Disorders, Inc.

383:
Glutaricaciduria I

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

     GA I
     Glutaric Acidemia I
     Glutaric Aciduria I
     Glutaricacidemia I
     Glutaryl-CoA Dehydrogenase Deficiency
     Dicarboxylic Aminoaciduria
     Glutaurate-Aspartate Transport Defect

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

     Glutaricaciduria IIA (GA IIA)
     Glutaricaciduria IIB (GA IIB)

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.

Glutaricaciduria is a rare hereditary metabolic disorder, caused by a
deficiency of the enzyme glutaryl-CoA dehydrogenase.  One of a group of
disorders known as "organic acidemias", it is characterized by decreased
muscle tone (hypotonia), vomiting, and excess acid in the blood.  The patient
may also have involuntary movements of the trunk and limbs (dystonia or
athetosis) and mental retardation may also occur.

Symptoms

Babies with Glutaricaciduria usually appear normal at birth.  During the
first year of life decreased muscle tone (hypotonia), vomiting, and acidity
of the blood may occur.  Taking on strange positions due to disordered muscle
tone (dystonia), involuntary and ceaseless slow, sinuous, writhing
(athetotic) or jerky (choreic) movements of the trunk and limbs may also
occur in combination with mental retardation.

Elevated concentrations of glutaric acid, beta-hydroxy-glutaric acid and
occasionally glutaconic acid appears in the urine of children with this
disorder.  Excretion of glutaric acid in the urine may exceed 1 gram per day,
an excessive amount.  Glutaric acid concentrations are also elevated in blood
serum, cerebrospinal fluid, and body tissues.  Some of these patients may
have unusual facial features (dysmorphia).  A type of spasm in which the head
and the heels are bent backward while the trunk is bowed forward
(opisthotonus) may also occur.

Causes

Glutaricaciduria is an autosomal recessive hereditary disorder caused by a
deficiency of the enzyme glutaryl-CoA dehydrogenase.  Accumulation of 5-
carbon dicarboxylic acids may impair synthesis of gamma-aminobutyric acid
(GABA) which functions as a neurotransmitter in the brain, inhibiting nerve
excitation.

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

Glutaricaciduria is a very rare inborn error of metabolism that affects males
as often as females.  There may be less than 100 cases of this type of
organic aciduria in the United States.

Related Disorders

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

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".  (For more information on this disorder, choose
"Glutaricaciduria II" as your search term in the Rare Disease Database.)

Therapies:  Standard

Glutaricaciduria is diagnosed when excessive glutaric acid is found in the
urine or by analysis of the deficient enzyme in white blood cells
(leukocytes).  Detection of the disorder in a fetus may be possible by
testing for the enzyme glutaryl CoA dehydrogenase.  It is imperative to test
for this disorder as soon after birth as possible.  Peritoneal dialysis
hemodialysis may be necessary.  The usefulness of restricting the amino acids
lysine, hydroxylysine, and tryptophan (which generate glutaric acid when they
are metabolized), 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 of 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

Glutaricaciduria has been treated on an experimental basis with a low protein
diet, riboflavin and Lioresal, a gamma-aminobutyric acid (GABA)-analog.  Diet
and riboflavin has had a slight-to-moderate effect on the clinical symptoms.
The excretion of glutaric acid and 2-amino-adipic acid in the urine decreased
considerably during this treatment.  Some neurological symptoms regressed
during treatment with Lioresal.  Although this treatment is experimental,
some researchers suggest that patients with Glutaricaciduria should be
treated as early as possible with this method.  However, long-term effects
are unknown.

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

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

to see if further patients are needed for this study.

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 I, 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

     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 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

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.

TREATMENT OF GLUTARYL-CoA DEHYDROGENASE DEFICIENCY (GLUTARIC ACIDURIA).
EXPERIENCE WITH DIET, RIBOFLAVIN, AND GABA ANALOG:  N.J. Brandt, et al.;
Journal of Pediatrics (April 1979:  issue 94,4).  Pp. 669-673.