CD-ROM Today 1996 January/CD-ROM Today 1996 January.iso/dp/0377/03771.txt

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$Unique_ID{BRK03771}
$Pretitle{}
$Title{Gilbert Syndrome}
$Subject{Gilbert Syndrome Gilbert's Disease Gilbert-Lereboullet Syndrome
Constitutional Liver Dysfunction Hyperbilirubinemia 1 Unconjugated Benign
Bilirubinemia Icterus Intermittens Juvenilis Familial Jaundice Meulengracht's}
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Copyright (C) 1990 National Organization for Rare Disorders, Inc.

317:
Gilbert Syndrome

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

Synonyms

     Gilbert's Disease
     Gilbert-Lereboullet Syndrome
     Constitutional Liver Dysfunction
     Hyperbilirubinemia 1
     Unconjugated Benign Bilirubinemia
     Icterus Intermittens Juvenilis
     Familial Jaundice
     Meulengracht's

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.


One of a benign group of metabolic abnormalities, Gilbert Syndrome is a
hereditary disorder involving a defect in the clearance of bile pigment
(bilirubin) from the liver.  This syndrome is common but innocuous and
easily controllable.  It is marked by a persistent yellow skin coloration
(jaundice) which may fluctuate in severity.

Symptoms

The onset of Gilbert Syndrome is shortly after birth, but may not be
recognized for many years.  A mild jaundice will appear at about age ten and
is more common in males than females.  There is a general lack of awareness
of the jaundice initially.  The jaundice may increase stress, strain, and
exposure to cold; fatigue, nausea, abdominal pain, and, rarely, diarrhea may
also occur.

The mild jaundice may be especially evident on the face, palms, and
soles of the feet (plantar) surfaces.  Formation of pigmented skin
thickenings similar to moles (nevi) and soft yellow spots (xanthelasma) on
eyelids can occur.  An increase in pigmentation on exposure to light and
heat are other symptoms of this liver disorder.  Slowing of the heartbeat
(bradycardia), low body temperature (hypothermia), neuromuscular
hypersensitivity, and migraine headaches may also be present.  Enlargement
of the liver and spleen are rarely seen.

Symptoms and jaundice become more pronounced following exertion, alcohol
intake, and/or intercurrent infections.  A slight reduction of red cell
survival is found in fifty percent of patients.

Causes

Gilbert Syndrome is inherited as an autosomal dominant disease, but a clear
genetic pattern is often hard to establish.  A misdiagnosis of chronic
hepatitis is sometimes made.  (In autosomal dominant disorders, a single
abnormal gene, contributed by either parent, "overrides" the normal gene
contributed by the other parent causing disease.  Individuals with one
affected parent have a 50% chance of inheriting the disorder.  Males and
females will be affected in equal numbers.)

A defect in uptake and clearance of unconjugated bilirubin from plasma
by the liver is a possible cause of this disorder.  Attempts to find a
consistent impairment of bilirubin conjugation or decrease of glycuronyl
transferase activity have failed.  Reduced bilirubin uridine diphosphate
(UDP) glucuronyl transferase activity could possibly explain
hyperbilirubinemia and impaired clearance of pigment, but it is not the only
mechanism responsible for the syndrome.

Affected Population

Gilbert Syndrome affects both sexes, but is more common in males, appearing
at about the age of ten years.  The male to female ration is 4:1.

Related Disorders

Dubin-Johnson syndrome is due to an inborn error of metabolism, and is an
autosomal recessive disorder.  There is a defect in excretion of conjugated
bile pigment (bilirubin) by the liver, and other organic metabolic
dysfunction.  Usually no noticeable symptoms appear (asymptomatic), except
for vague gastrointestinal complaints and mild chronic or intermittent
jaundice.

Rotor Syndrome is a variant of Dubin-Johnson syndrome.  Less frequent
than Dubin-Johnson, it is also usually mild and involves much the same
symptoms.  These include occasions of pain in the right upper quadrant and
mild jaundice.  Enlargement of the liver may also occur.  The prognosis is
generally favorable.

Crigler-Najjar syndrome is a congenital non-hemolytic jaundice in
infants.  This is a very rare disease that can be inherited through both
dominant and recessive traits.  The dominant type involves a later onset of
jaundice, an absence of eye problems or destructive changes in the brain.
The recessive form usually involves severe deep jaundice from birth, a
visual disorder, and some changes in the brain function.

Hyperbilirubinemia, Arias Type, is a less severe type of liver
dysfunction which differs from similar disorders in mode of inheritance,
lack of brain damage, and favorable prognosis.

Therapies:  Standard

In Gilbert Syndrome, phenobarbitol reduces the bile pigment (bilirubin)
level and jaundice decreases.  Careful regulation of the diet is important
as fasting increases hyperbilirubinemia.  Prognosis is good since the
disease is benign.

Therapies:  Investigational

Research has been done on Gilbert Syndrome patients to determine the
impairment of bile pigment (bilirubin) uptake or decrease of glucuronyl
transferase activity.  Understanding these mechanisms could lead to new
forms of treatment.

Clinical trials of the orphan drug flumecinol (Zixoryn) for treatment of
hyperbilirubinemia, a symptom of Gilbert Syndrome, in infants who are
unresponsive to phototherapy are being conducted.  For more information,
physicians can contact:

     Farmacon, Inc.
     P.O. Box 586
     Westport, CT 06881

For information on additional therapies that have been designated as
Orphan Drugs in the last few months, please return to the main menu of NORD
Services and access the Orphan Drug Database.

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

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

     American Liver Foundation
     998 Pompton Ave.
     Cedar Grove, NJ  07009
     [phone]
     [phone]

     The United Liver Foundation
     11646 West Pico Blvd.
     Los Angeles, CA  90064
     [phone] or 445-4200

     Children's Liver Foundation
     14245 Ventura Blvd.
     Sherman Oaks, CA  91423
     [phone]

     National Digestive Diseases Information Clearinghouse
     Box NDIC
     Bethesda, MD  20892
     [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

MENDELIAN INHERITANCE IN MAN, 6th ed.:  Victor A. McKusick; Johns Hopkins
University Press, 1983; P. 283.

Berk, P.D.; Martin, J.F.; Blaschke, T.F.; Scharschmidt, B.F.; Plotz, P.H.
Unconjugated Hyperbilirubinemia:  Physiologic Evaluation and Experimental
Approaches to Therapy.  ANN INTERN MED 1975 April:82(4):552-570.