$Unique_ID{BRK03937} $Pretitle{} $Title{Leukodystrophy, Krabbe's} $Subject{Leukodystrophy Krabbe's Galactocerebrosidase Deficiency Galactoside Beta-Galactosidase Deficiency Galactosylceramidase Deficiency Galactosyl Ceramide Lipidosis Globoid Leukodystrophy Krabbe's Disease Leukodystrophy Globoid Cell Sphingolipidosis Adrenoleukodystrophy Canavan's Leukodystrophy Metachromatic Leukodystrophy Alexander's Disease } $Volume{} $Log{} Copyright (C) 1987, 1988, 1990 National Organization for Rare Disorders, Inc. 379: Leukodystrophy, Krabbe's ** IMPORTANT ** It is possible the main title of the article (Krabbe's Leukodystrophy) 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 Galactocerebrosidase Deficiency Galactoside Beta-Galactosidase Deficiency Galactosylceramidase Deficiency Galactosyl Ceramide Lipidosis Globoid Leukodystrophy Krabbe's Disease Leukodystrophy, Globoid Cell Sphingolipidosis Information on the following diseases can be found in the Related Disorders section of this report: Adrenoleukodystrophy Canavan's Leukodystrophy Metachromatic Leukodystrophy Alexander's Disease 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. Krabbe's Leukodystrophy is a very rare hereditary lipid storage disorder caused by a deficiency of the enzyme galactoside beta-galactosidase (galactosyl-ceramidase). This causes the myelin sheath surrounding nerves in the brain to degenerate (demyelination). Characteristic globoid cells appear in affected areas of the brain. This metabolic disorder is characterized by progressive neurological dysfunction such as mental retardation, paralysis, blindness, deafness and pseudobulbar palsy. Symptoms Onset of Krabbe's Leukodystrophy in the predominant infantile form (90% of cases) occurs between 3 and 5 months of age. A late-onset form of the disorder occurs at 18 months or a later age. Infants affected by Krabbe's Leukodystrophy are fretful and apathetic. Vomiting and partial unconsciousness are other possible symptoms. The lower extremities may have spastic contractions. Seizures characterized by alternating contraction and relaxation (clonic), or by continuous tension (tonic), may also occur. Affected infants are hypersensitive to sounds and noises. Mental and physical development may be slow. Because of degeneration of certain parts of the brain, the legs are sometimes rigidly extended at the hip and knee; the arms may be rotated at the shoulder and extended at the elbow; and the ankles, toes and fingers may be flexed (decerebrate rigidity). Blindness caused by brain cortex degeneration may also occur. Patients with Krabbe's Leukodystrophy may also have difficulty swallowing (dysphagia). Causes Krabbe's Leukodystrophy is a hereditary disorder transferred to offspring through recessive genes. It is caused by a deficiency of the enzyme galactoside beta-galactosidase (galactosyl ceramidase). This enzyme is needed for the metabolism of galactocerebroside (galactosyl ceramide), a component of the fatty sheath around the nerves (myelin). The demyelination of the nerve cells in the large hemispheres of the brain (and in the brain stem) causes the neurological symptoms of Krabbe's Leukodystrophy. 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 About 1 in 40,000 newborn babies in the United States is affected with Krabbe's Leukodystrophy. Males are affected as often as females. Related Disorders There are many related forms of Leukodystrophy. For more information on these disorders, choose "Leukodystrophy" as your search term in the Rare Disease Database. Adrenoleukodystrophy (ALD, or Schilder's Disease) is one of many different leukodystrophies. The disorder may appear in two distinct genetic forms: sex-linked and Neonatal ALD. Both are characterized by destruction of the lipid sheaths surrounding the nerves (demyelination) in the brain. However, they differ in the mode of inheritance, severity and type of symptoms. All types of ALD are characterized by an accumulation of Very Long Chain Fatty Acids (VLCFA), which is a type of fat molecule that accumulates in the body's tissues, especially in the adrenal gland and the white matter of the brain. An accumulation of lymph and plasma cells around the blood vessels in the central nervous system may also occur. Canavan's Leukodystrophy (Spongy Degeneration of the Brain) is a form of leukodystrophy which causes the white matter of the brain to be replaced by microscopic fluid-filled spaces. This disorder, a hereditary disease in children, is characterized by structural abnormalities and deterioration of motor, sensory, and intellectual functions. It seems to affect persons of Eastern European Jewish ancestry most frequently. The disorder is progressive and degenerative. Metachromatic Leukodystrophy (MLD) is an autosomal recessive inherited disease which affects the brain and spinal cord. The disease is characterized by progressive paralysis and dementia. Alexander's Disease is an infantile form of leukodystrophy characterized by an enlarged brain, mental retardation, failure to thrive, spasticity and possibly seizures. For more information on the above disorders, choose "Adrenoleukodystrophy," "Canavan," "MLD," and "Alexander" as your search terms in the Rare Disease Database. Therapies: Standard Krabbe's Leukodystrophy can be diagnosed by testing the activity of the enzyme galactocerebrosidase (galactosylceramidase) in fibroblast cells obtained from an infant or from a fetus by amniocentesis. Treatment for Krabbe's Leukodystrophy is symptomatic and supportive. Genetic counseling may be helpful for families of children affected by this illness. Therapies: Investigational Current research is directed toward the identification and cloning of genes, and defining the specific gene abnormality responsible for the leukodystrophy. Bone marrow transplantation is being researched as a possible treatment for Krabbe's Leukodystrophy patients. This involves extracting cross-matched bone marrow from a healthy donor and injecting it into a patient. The healthy bone marrow cells enter the general circulation and migrate through the blood to marrow cavities in the patient's bones. The new marrow cells begin to grow and produce new white blood cells and platelets. This procedure involves risks which must be balanced against possible benefits. It is used experimentally in the most severe cases of this disorder. Bone marrow transplantation is being tested as a treatment for infantile Krabbe's Leukodystrophy. Bone marrow transplantation is not recommended for patients with relatively advanced neurological symptoms. More research is needed to determine the safety and effectiveness of this procedure. This disease entry is based upon medical information available through March 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 Krabbe's Leukodystrophy, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 United Leukodystrophy Foundation 2304 Highland Drive Sycamore, IL 60178 (815) 895-3211 (800) 728-5483 Adrenoleukodystrophy (ALD) Project Hugo M. Moser, M.D. John F. Kennedy Institute 707 North Broadway Baltimore, MD 21205 (301) 522-5405 NIH/National Institute of Neurological Disorders & Stroke (NINDS) 9000 Rockville Pike Bethesda, MD 20892 (301) 496-5751 (800) 352-9424 Research Trust for Metabolic Diseases in Children Golden Gates Lodge, Weston Rd. Crewe CW1 1XN, England Telephone: (0270) 250244 Association Europeenne contre les Leucodystrophies 7 Rue Pasteur 54000 NANCY France For more information on genetics and genetic counseling referrals, please contact: 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 A CORRELATIVE SYNOPSIS OF THE LEUKODYSTROPHIES: P. Morell; Neuropediatrics (September 1984: Suppl. 15). Pp. 62-65. PRENATAL DIAGNOSIS OF KRABBE DISEASE USING A FLUORESCENT DERIVATIVE OF GALACTOSYLCERAMIDE: M. Zeigler, et al.; Clinica Chimica Acta (October 15, 1984: issue 142,3). Pp. 313-318.