$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 (212) 430-2091 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 (510) 596-6916 or Dr. Packman at (415) 476-4337. 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, (301) 496-9101. 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 (203) 746-6518 Corporation for Menkes' Disease 5720 Buckfield Court Fort Wayne, IN 46815 (219) 436-0137 NIH/National Institute of Neurological Disorders & Stroke (NINDS) 9000 Rockville Pike Bethesda, MD 20892 (301) 496-5751 (800) 352-9424 For Genetic Information and genetic counseling referrals: March of Dimes Birth Defects Foundation 1275 Mamaroneck Avenue White Plains, NY 10605 (914) 428-7100 Alliance of Genetic Support Groups 35 Wisconsin Circle, Suite 440 Chevy Chase, MD 20815 (800) 336-GENE (301) 652-5553 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.