$Unique_ID{BRK03768} $Pretitle{} $Title{Gaucher Disease} $Subject{Acid Beta-glucosidase deficiency Familial Splenic Anemia Cerebroside Lipidosis Cerebrosidosis Gaucher-Schlagenhaufer Glucocerebrosidase deficiency Glucocerebrosidosis Glucosyl Ceramide Lipidosis Histiocytosis, lipid, kerasin type Norrbottnian Gaucher Disease Type I Gaucher Disease also known as Non-Neuronopathic Chronic, Adult Gaucher Disease or Noncerebral Juvenile Gaucher Disease Type II Gaucher Disease also known as Neuronopathic Acute or Infantile Gaucher Disease Type III Gaucher Disease also known as Subacute Neuronopathic, Juvenile Sandhoff Disease Hajdu-Cheney Syndrome Hepatic Fibrosis, Congenital Osteonecrosis} $Volume{} $Log{} Copyright (C) 1984, 1985, 1986, 1987, 1988, 1989, 1990, 1992, 1993 National Organization for Rare Disorders, Inc. 12: Gaucher Disease ** IMPORTANT ** It is possible that the main title of the article (Gaucher Disease) is not the name you expected. Please check the SYNONYMS listing to find the alternate name and disorder subdivisions covered by this article. Synonyms Acid Beta-glucosidase deficiency Familial Splenic Anemia Cerebroside Lipidosis Cerebrosidosis Gaucher-Schlagenhaufer Glucocerebrosidase deficiency Glucocerebrosidosis Glucosyl Ceramide Lipidosis Histiocytosis, lipid, kerasin type Norrbottnian Gaucher Disease DISORDER SUBDIVISIONS: Type I Gaucher Disease also known as Non-Neuronopathic Chronic, Adult Gaucher Disease or Noncerebral Juvenile Gaucher Disease Type II Gaucher Disease also known as Neuronopathic Acute or Infantile Gaucher Disease Type III Gaucher Disease also known as Subacute Neuronopathic, Juvenile Gaucher Disease, or Adult Cerebral Gaucher Disease Information on the following diseases can be found in the Related Disorders section of this report: Sandhoff Disease Hajdu-Cheney Syndrome Hepatic Fibrosis, Congenital Osteonecrosis 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. Gaucher disease is the most common of the lipid storage diseases (which include Tay-Sachs, Fabry's, and Neimann-Pick diseases). Lipids are various fats or fat-like substances in the body. Lipids are stored by the body to be used as energy at a later time. There are three forms of Gaucher disease: Type I (nonneuroleptic); Type II (acute neuroleptic, or infantile cerebral); Type III (subacute neuroleptic). Major symptoms include a swollen abdomen, bone deterioration and acute attacks of bone pain. Symptoms In Type I Gaucher disease, bone deterioration is the most common symptom. Other symptoms include gross enlargement of the liver (hepatomegaly) and/or the spleen (splenomegaly) and a low level of iron in the red blood cells (anemia). People with Gaucher disease usually appear to have a very swollen abdomen due to enlarged internal organs. In Type II Gaucher disease, patients may have an enlarged liver and/or spleen and symptoms that involve the central nervous system (neurological manifestations). The symptoms may include overextension (hyperextension) of the neck, a stiff neck, general feeling of tiredness, and an inability to move and respond appropriately to outside stimulus (catatonia). The eyes may be crossed (strabismus) and there may be an increase in the deep reflexes of the body. Patients with Type II Gaucher may also have muscle spasms in the voice box (laryngismus). Mental retardation may also be present. In Type III Gaucher disease, patients usually experience symptoms that are similar to those of Type I but also include central nervous system symptoms. These may include seizures, mental retardation, and abnormal movements of the eyes, arms, legs, and head. A diagnostic test is available to detect affected people and carriers of this disorder. This condition may also be diagnosed in pregnant women by testing the cells in the fluid that surrounds the fetus (amniocentesis). Causes Most types of Gaucher disease are inherited as an autosomal recessive trait. Symptoms develop due to a failure to produce a sufficient amount of the enzyme glucocerebrosidase. All three different types of Gaucher disease are characterized by the presence of fat laden "Gaucher cells". As seen under a microscope, the cells appear very large and round and have the appearance of wrinkled tissue paper or "crumpled silk". The defective gene that causes Gaucher disease and controls the enzyme glucocerebrosidase is thought to be located at the q21-q31 region of chromosome 1. It is thought that different mutations in this gene are associated with different types of Gaucher disease. In 1991 an atypical autosomal dominant form of Gaucher was identified in a female patient. 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 for the same trait 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 not show 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. In dominant disorders, a single copy of the disease gene (received from either the mother or father) will be expressed "dominating" the normal gene and resulting in appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.) Affected Population Gaucher disease Type I affects males and females in equal numbers. Onset can be at any age although most people are in their late teens when they are initially diagnosed. A high proportion of Ashkenazi Jews are affected with this disorder. Type II Gaucher disease is a rarer form with symptoms that usually appear in the first few months of life. Both males and females can have this disorder although a slightly higher number of males are diagnosed than females. Type III is the rarest form of Gaucher disease. The age of onset can be highly variable but generally begins in during childhood or adolescence. Both sexes can be affected. It has been estimated that all types of Gaucher disease together may affect between 20,000 to 40,000 people worldwide. Related Disorders Symptoms of the following disorders can be similar to those of Gaucher disease. Comparisons may be useful for a differential diagnosis: Sandhoff Disease is a severe form of Tay-Sachs disease. It is a progressive, inherited, lipid storage disorder that leads to the destruction of the central nervous system. The first symptoms usually occur in the third to sixth month of life. These symptoms may include feeding problems, general tiredness (lethargy) and a marked "startle" response to sounds. Cherry red spots are usually seen on the skin. (For more information on this disorder, choose "Sandhoff Disease" as your search term on the Rare Disease Database). Hajdu-Cheney Syndrome is a rare disorder that affects the tissue that supports and joins other body tissue and organs (connective tissue). The most distinctive symptom of this disorder is a condition in which the palms of the hands and the soles of the feet have ulcerating tissue (lesions). This occurs along with a softening and destruction of the bones. There may also be abnormal development of other bones, joints and teeth. There is a decrease in bone mass and changes in the skull and jawbone. (For more information on this disorder, choose "Hajdu-Cheney" as your search term in the Rare Disease Database). Hepatic Fibrosis (Congenital) is a rare inherited disorder that affects both the liver and the kidneys. The symptoms, which usually occur in childhood, may include a swollen abdomen, a firm enlarged liver (hepatomegaly), and the vomiting of red blood due to bleeding in the stomach and intestines. Although liver function tests are usually normal, a biopsy can reveal the presence of fiberlike connective tissue that spreads through the liver. (For more information on this disorder, choose "Hepatic Fibrosis" as your search term in the Rare Disease Database). OSTEONECROSIS is a slowly progressive disorder of bone destruction. It is often due to inadequate blood supply to a bone. The ends of the long bones are the most commonly affected (i.e. femur and humerus). This disorder may cause pain in the hips, knees, and shoulders. This pain generally occurs when standing, walking or lifting. The pain may worsen and eventually be present during rest or sleep. Other symptoms may include muscle spasms, joint stiffness, and a limitation of range of movement. (For more information on this disorder, choose "Osteonecrosis" as your search term in the Rare Disease Database). Therapies: Standard Treatment of Gaucher Disease may involve the removal of the spleen (splenectomy) if circumstances warrant it. Joint replacements for hips, knees, ankles, shoulders, elbows and wrists may also be considered if bone destruction has occurred. The orphan drug Ceredase (glucocerebrosidase/beta-glucosidase), which is a placenta-derived enzyme, was approved by the FDA in April 1991 for the treatment of Type I Gaucher disease. For further information physicians may contact: Genzyme Corp. 75 Kneeland St. Boston, MA 02111 (800) 332-1042 Genetic counseling and testing may be of benefit for patients and their families. Therapies: Investigational Dr. Edward Ginns is developing a biotechnology version of the enzyme (PEG- glucocerebrosidase) that may last longer in the body, thereby reducing the cost to people with Gaucher Disease. Dr. Ginns is searching for patients who are not taking Ceredase who might be interested in participating in this clinical trial. For more information, please contact: Dr. Edward Ginns Section on Molecular Neurogenetics, Clinical Neuroscience Branch Bldg. 10, Rm. 4N214 NIH/National Intstitute of Mental Health (NIMH) Bethesda, MD 20892 (301) 496-0373 A clinical research program has been established at the National Institutes of Health in Bethesda, Maryland, to study neurogenetic and lysosomal storage disorders. Gaucher Disease is a high priority of this group of diseases, including mucopolysaccharidoses, glycogen storage disorders, and other related neurogenetic diseases. The goal of this program is to further the fundamental understanding of inherited diseases as an approach to improved diagnosis and treatment. Patients included in these studies may be evaluated at the Genetics Clinic as well as the Molecular Neurogenetics Unit, Clinical Neuroscience Branch, National Institute of Mental Health (NIMH), and the Human Genetics Branch of the National Institute of Child Health and Human Development (NICHHD). For further information, please contact: Patient Care Coordinator Human Genetics Branch NIH/National Institute of Child Health and Human Development (NICHD) Bethesda, MD 20892 (301) 496-7661 Research is ongoing in the areas of recombinant DNA, bone marrow transplantation, gene therapy and enzyme replacement therapy, the mechanism of action of the heat-stable activator protein, and cloning. A new form of the enzyme is being developed through biotechnological engineering, and is being tested in clinical trials. Contact: NIH/National Institutes of Health Building 10, Rm. 4N248 9000 Rockville Pike Bethesda, MD 20982 (301) 496-1465 Bone marrow transplantation is being tested as a treatment for Gaucher Disease. 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 treatment. Other clinical research is being pursued at: University of Pittsburgh Medical School Dept. of Biochemistry Pittsburgh, PA 15261 (412) 624-2505 Att: Robert Glew, M.D. RESEARCH: Characterization of lipid requirements of enzymes and investigation of the mechanism of action of the heat-stable activator protein. Scripps Research Institute 10666 N. Torrey Pine Road La Jolla, CA 92037 (619) 455-9100 Att: Ernest Beutler, M.D. RESEARCH: Studying protein defects of enzymes using antibodies and monoclonal antibodies, cloning enzyme genes, developing method for introducing genes back into protein's cells, and treating patients with low doses of Ceredase. Mount Sinai Hospital Division of Medical Genetics Annenberg Building, Room 17-76 100th Street and 5th Avenue New York, NY 10029 Att: Robert Desnick, M.D. RESEARCH: Replacement enzymes in bone marrow transplantations. Robert E. Lee, M. D. of the University of Pennsylvania is compiling a database dealing with the disease. Contact: University of Pittsburgh Medical School Dept. of Pathology Pittsburgh, PA 15261 Att: Robert E. Lee, M. D. Research on birth defects and their causes is ongoing. The National Institutes of Health (NIH) is sponsoring the Human Genome Project which is aimed at mapping every gene in the human body and learning why they sometimes malfunction. It is hoped that this new knowledge will lead to prevention and treatment of genetic disorders in the future. A clinical trial using human glucocerebrosidase for treatment of Gaucher's Disease is being organized by Drs. Ellen Sidransky and Edward Ginns at NIMH. The PEG-glucocerebrosidase is being developed by Enzon, Inc., and has received orphan drug status. It is hoped that PEG-glucocerebrosidase will lead to a decrease in symptoms. For further information, please contact: Ms. E. Alzona, Clinical Neuroscience Branch Bldg. 10, Rm. 3N 256 9000 Rockville Pike Bethesda, MD 20892 (301) 496-0373 FAX (301) 402-6438 This disease entry is based upon medical information available through March 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 Gaucher disease, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 Gaucher Disease Foundation 19241 Montgomery Village Ave., Suite E21 Gaithersburg, MD 20879 (301) 990-3800 Tay-Sachs & Allied Diseases Association, Inc. 2001 Beacon Street, Rm. 304 Brookline, MA 02164 (617) 277-4463 or (617) 277-3965 NIH/National Institute of Neurological Disorders & Stroke (NINDS) 9000 Rockville Pike Bethesda, MD 20892 (301) 496-5751 (800) 352-9424 For 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 MENDELIAN INHERITANCE IN MAN, 9th Ed.: Victor A. McKusick, Editor: Johns Hopkins University Press, 1990. Pp. 1200-1204. CECIL TEXTBOOK OF MEDICINE, 19th Ed.: James B. Wyngaarden, and Lloyd H. Smith, Jr., Editors; W.B. Saunders Co., 1990. Pp. 1091-1092. BIRTH DEFECTS ENCYCLOPEDIA, Mary Louise Buyse, M.D., Editor-In-Chief; Blackwell Scientific Publications, 1990. Pp. 769-770. GAUCHER'S DISEASE: NEW MOLECULAR APPROACHES TO DIAGNOSIS AND TREATMENT, E. Buetler; Science (May 1992; 256 (5058)): Pp. 794-799.