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$Unique_ID{BRK03998}
$Pretitle{}
$Title{Menkes' Disease}
$Subject{Menkes' Disease Steely Hair Disease Kinky Hair Disease
Trichopoliodystrophy X-linked Copper Malabsorption X-linked Copper Deficiency
Wilson's Disease Primary Biliary Cirrhosis Indian Childhood Cirrhosis }
$Volume{}
$Log{}

Copyright (C) 1989, 1992, 1993 National Organization for Rare Disorders,
Inc.

603:
Menkes' Disease

** IMPORTANT **
It is possible that the main title of the article (Menkes' Disease) is
not the name you expected.  Please check the SYNONYM listing to find the
alternate names and disorder subdivisions covered by this article.

Synonyms

     Steely Hair Disease
     Kinky Hair Disease
     Trichopoliodystrophy
     X-linked Copper Malabsorption
     X-linked Copper Deficiency

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

     Wilson's Disease
     Primary Biliary Cirrhosis
     Indian Childhood Cirrhosis

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.


Menkes' Disease is a genetic disorder of copper metabolism beginning
before birth.  Copper accumulates in excessive amounts in the liver, and is
deficient in most other tissues of the body.  Structural changes occur in the
hair, brain, bones, liver and arteries.

Symptoms

Menkes' Disease primarily affects males and is characterized by stubby,
tangled, sparse, steely or kinky hair that is easily broken.  The hair is
often white, ivory, or gray in color.  Unusual facial features include pudgy
cheeks and abnormal eyebrows.  Affected infants are often born prematurely.
Lower than normal body temperature (hypothermia) and excess bilirubin in the
blood (hyperbilirubinemia) may occur causing a yellow appearance (jaundice).
Hypothermia may also occur in older infants.  In some cases, early symptoms
may resolve, and normal or slightly slowed development may proceed for two to
three months.  At approximately three months of age, severe developmental
delay, loss of early development skills, and convulsions may occur.  Brain
abnormalities such as a blood clot at the base of the brain (subdural
hematoma) and/or rupture or thrombosis of arteries in the brain may occur.
Spastic dementia and seizures may eventually arise.  Weakened bones
(osteoporosis) due to abnormal copper metabolism can result in fractures.
The combination of subdural hematoma and bone fractures may lead to an
incorrect diagnosis of child abuse.  Emphysema, bladder abnormalities,
degeneration of the retina and cysts of the iris have also been described.
In some cases, symptoms may be very mild and only a few typical symptoms may
appear.

Causes

Menkes' Disease is inherited as an X-linked recessive trait.  (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.  X-linked recessive disorders are conditions which are coded on the X
chromosome.  Females have two X chromosomes, but males have one X chromosome
and one Y chromosome.  Therefore, in females, disease traits on the X
chromosome can be masked by the normal gene on the other X chromosome.  Since
males only have one X chromosome, if they inherit a gene for a disease
present on the X, it will be expressed.  Men with X-linked disorders transmit
the gene to all their daughters, who are carriers, but never to their sons.
Women who are carriers of an X-linked disorder have a fifty percent risk of
transmitting the carrier condition to their daughters, and a fifty percent
risk of transmitting the disease to their sons.)

Affected Population

An Australian study of Menkes' Disease from 1966 to 1971 suggested an
incidence of 1 in 35,500 live births.  A 1980 study modified this figure to 1
in 90,000 live births.  Other scientists estimate the number of cases to be
approximately 1 in 50,000 to 1 in 100,000.

Related Disorders

Symptoms of the following disorders can be similar to those of Menkes'
Disease.  Comparisons may be useful for a differential diagnosis:

Wilson's Disease is a rare genetic disorder of copper metabolism
characterized by excess storage of copper in the body tissues, particularly
in the liver, brain and corneas of the eyes.  It leads eventually to liver
disease, brain dysfunction, and a characteristic rusty-brown colored ring
around the cornea of each eye known as a Kayser-Fleischer ring.  Symptoms
usually do not appear in early infancy and patients do not have the
characteristic kinky hair of Menkes' Disease.  (For more information on this
disorder, choose "Wilson" as your search term in the Rare Disease Database).

Primary Biliary Cirrhosis (PBC), also known as Hanot's Cirrhosis, is a
rare condition occurring mainly in women.  Four pathologic stages occur in
increasing severity.  Gradual deterioration of the small bile ducts inside
the liver causes a blockage in the flow of bile (cholestasis) and liver
enlargement.  In time, retention of chemicals in the liver cause further
damage.  Bile acids are absorbed abnormally from the liver into the blood and
soft tissues, causing itching accompanied by yellow skin discoloration
(jaundice).  Dietary and bone problems can also result.  Copper retention in
the liver, also present in Menkes' Disease, can also occur.  (For more
information on this disorder, choose "PBC" as your search term in the Rare
Disease Database).

Indian Childhood Cirrhosis is a familial and probably genetically
determined disease.  An extremely large amount of copper accumulates in the
liver, similar to that of Menkes' Disease.

Therapies:  Standard

Prenatal diagnosis of Menkes' Disease and various forms of intravenous or
oral copper supplementation begun early may be of some benefit.  Copper
nitriloacetate is the only form of copper that has proved to be absorbed from
the intestine in Menkes' Disease patients.  Genetic counseling may be
recommended for patients and their families.  Other treatment is symptomatic
and supportive.

Therapies:  Investigational

Research on Menkes' Disease is aimed at the discovery of a form of copper
which can bypass the disturbance in copper transport and deliver the copper
to the enzymes that require it, especially in the brain.  Trials of monoamine
oxidase inhibitors are underway since some of the more serious effects of the
disease may be the result of defective catecholamine synthesis.  Studies of
the effects of Vitamin C on copper absorption are also underway to discover
methods of releasing some of the high accumulations of copper in the liver
and intestines.  However, more research is needed to determine long-term
effects of these experimental treatments.

An investigational treatment using the drug ethambutol is being tested by
the members of The Albert Einstein College of Medicine.  Doctors who wish to
enroll patients in the study may contact:

     Herbert Scheinberg or Janna C. Collins
     Albert Einstein College of Medicine
     1300 Morris Park Ave., Ullmann 517
     Bronx, NY  10461
     [phone]

Scientists are conducting genetic linkage studies to determine if Menkes'
Disease and X-linked Ehlers-Danlos are located at the same place on the same
gene.  These disorders tend to display similar problems with copper
metabolism.  Families with more than one affected male or carrier females
may wish to participate in studies to help determine the exact relationship
of the genetic linkage in the two disorders.  Interested persons may contact
Dr. Yang at [phone] or Dr. Packman at [phone].

Another researcher working on Menkes Disease is Dr. Stephan Kaler.  Dr.
Kaler is persuing his work at the National Institute of Health, Bldg. 10, Rm.
9S-242, 9000 Rockville Pike, Bethesda, MD, 20892, [phone].

This disease entry is based upon medical information available through
February 1993.  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 Menkes' Disease, please contact:

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

     Corporation for Menkes' Disease
     5720 Buckfield Court
     Fort Wayne, IN  46815
     [phone]

     NIH/National Institute of Neurological Disorders & Stroke (NINDS)
     9000 Rockville Pike
     Bethesda, MD  20892
     [phone]
     [phone]

For Genetic Information and genetic counseling referrals:

     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, 7th ed.:  Victor A. McKusick; Johns Hopkins
University Press, 1986.  Pp. 1414-1415.

THE METABOLIC BASIS OF INHERITED DISEASE, 5th Ed.:  John B. Stanbury, et
al., eds.; McGraw Hill, 1983.  Pp. 1251-1266.

METALLOTHIONEIN GENE REGULATION IN MENKES' SYNDROME:  D.H. Hamer; Arch
Dermatol (October 1987, issue 123 (10)).  Pp. 1384a-1385a.

LIFE-SPAN AND MENKES KINKY HAIR SYNDROME:  REPORT OF A 13-YEAR COURSE OF
THIS DISEASE:  C. Sander, et al.; Clin Genet (March 1988, issue 33 (3)).  Pp.
228-233.

MENKES SYNDROME IN A GIRL WITH X-AUTOSOME TRANSLOCATION:  S. Kapur, et
al.; Am J Med Genet (February 1987, issue 26(2)).  Pp.  503-510.

GENETIC DISEASES OF COPPER METABOLISM:  J.R. Prohaska; Clin Physiol
Biochem (1986, issue 4(1)).  Pp. 87-93.