CD-ROM Today (UK) (Spanish) 15/CDRT.iso/dp/0405/04055.txt

Text File | 1994-01-18 | 9.4 KB | 223 lines

$Unique_ID{BRK04055}
$Pretitle{}
$Title{Non-Ketotic Hyperglycinemia}
$Subject{Non-Ketotic Hyperglycinemia Glycinemia, Nonketotic Hyperglycinemia,
Nonketotic Acidemias, Methylmalonic Isovaleric Acidemia Glutaricaciduria II
Maple Syrup Urine Disease Propionic Acidemias}
$Volume{}
$Log{}

Copyright (C) 1988, 1989, 1990 National Organization for Rare Disorders,
Inc.

520:
Non-Ketotic Hyperglycinemia

** IMPORTANT **
It is possible the main title of the article (Non-Ketotic
Hyperglycinemia) 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

     Glycinemia, Nonketotic
     Hyperglycinemia, Nonketotic

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

     Acidemias, Methylmalonic
     Isovaleric Acidemia
     Glutaricaciduria II
     Maple Syrup Urine Disease
     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.


Non-Ketotic Hyperglycinemia is a genetic disorder characterized by an
error of amino acid metabolism.  Large amounts of the amino acid glycine tend
to accumulate in body fluids particularly in the cerebrospinal fluid.  The
metabolic block occurs in the conversion of glycine into smaller molecules.
Severe illness usually occurs soon after birth and many patients become
mentally retarded and/or develop seizure disorders.

Symptoms

Non-Ketotic Hyperglycinemia is characterized early in life by severe illness,
failure to thrive, low muscle tone (hypotonia), and drowsiness or lethargy.
Mental retardation may develop, relatively mild in some cases, but usually
severe.  Seizures, usually with jerking motions (myoclonus) may also occur.
The amount of glycine in blood, urine and cerebrospinal fluid is extremely
high.

Causes

Non-Ketotic Hyperglycinemia is an autosomal recessive hereditary disorder
caused by an impairment in the breakdown of the amino acid glycine.  (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

Non-Ketotic Hyperglycinemia is a rare metabolic disorder that affects infants
soon after birth.  Males and females are affected in equal numbers.

Related Disorders

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

Methylmalonic Acidemias are another type of organic acidemia.  All
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 (metabolic acidosis).  In acute cases, drowsiness, coma,
and/or seizures may occur.  Mental retardation is a long-term consequence.
The disorders 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 on this
disorder, 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 are forms of organic acidemia, a group of
metabolic disorders characterized by the presence of excess acid in the blood
and urine.

Glutaricaciduria IIA (Glutaric Acidemia IIA) is the neonatal onset form of
Glutaricaciduria.  It 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.

Glutaricaciduria IIB (Glutaric Acidemia IIB;  Ethylmalonic Adipicaciduria) is
the milder adult onset form of the disorder.  It is inherited as an autosomal
recessive trait.  Symptoms may include acidity of the body tissues (metabolic
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" as 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
sometimes 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 Disease" 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 later during infancy.  Without treatment,
dehydration, drowsiness, lethargy, vomiting, and in some cases, coma may
develop.  (For more information on this disorder, choose "Propionic Acidemia
as your search term in the Rare Disease Database.

Therapies:  Standard

Strychnine treatment for seizures has been a moderate success in a few cases
of Non-Ketotic Hyperglycinemia.  The tranquilizer diazepam and sodium
benzoate, in combination with choline and folic acid (vitamins of the B
complex) can sometimes also be beneficial to treat the seizures occurring in
this disorder.  Other treatment is symptomatic and supportive.

Genetic counseling is recommended for families of children with Non-
Ketotic Hyperglycinemia.

Therapies:  Investigational

Research on enzyme replacement therapy is ongoing.  It is possible that
treatment of Non-Ketotic Hyperglycinemia will be enhanced when scientists
learn how to replace or increase enzymes in children affected by enzyme
deficiencies.

This disease entry is based upon medical information available through
April 1990.  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 Non-Ketotic Hyperglycinemia, 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:

     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

THE METABOLIC BASIS OF INHERITED DISEASE, 5th ed.:  John B. Stanbury, et al.,
eds.;  McGraw Hill, 1983.  Pp. 561-569.

THE EFFECTIVENESS OF BENZOATE IN THE MANAGEMENT OF SEIZURES IN NONKETOTIC
HYPERGLICINEMIA:  J.A. Wolff, et al.; American Journal Dis Child (June 1986:
issue 140(6)).  Pp. 596-602.

NONKETOTIC HYPERGLYCINEMIA:  TREATMENT WITH DIAZEPAM--A COMPETITOR FOR
GLYCINE RECEPTORS:  R. Matalon, et al.; Pediatrics (April 1983:  issue 71(4)).
Pp. 581-584.