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- $Unique_ID{BRK04214}
- $Pretitle{}
- $Title{Severe Combined Immunodeficiency}
- $Subject{Severe Combined Immunodeficiency SCID Autosomal recessive SCID
- Adenosine deaminase (ADA) deficiency ADA Deficiency X-linked recessive SCID
- Bare lymphocyte syndrome SCID with leukopenia reticular dysgenesis}
- $Volume{}
- $Log{}
-
- Copyright (C) 1986, 1987, 1988, 1989, 1990, 1992 National Organization
- for Rare Disorders, Inc.
-
- 77:
- Severe Combined Immunodeficiency
-
- ** IMPORTANT **
- It is possible that the main title of the article (Severe Combined
- Immunodeficiency) is not the name you expected. Please check the SYNONYM
- listing to find the alternate names and disorder subdivisions covered by this
- article.
-
- Synonyms
-
- SCID
-
- DISORDER SUBDIVISIONS:
-
- Autosomal recessive SCID
- Adenosine deaminase (ADA) deficiency
- ADA Deficiency
- X-linked recessive SCID
- Bare lymphocyte syndrome
- SCID with leukopenia, also known as reticular dysgenesis
-
- 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.
-
-
- Severe Combined Immunodeficiency (SCID) comprises a group of congenital
- syndromes in which there appears to be no adaptive immune function whatever.
- Both the ability to acquire immunity (cell mediated immunity) and to form
- antibodies (humoral immunity) are absent. Thus the patient lacks all
- resistance against bacteria, viruses, fungi, and other infectious agents.
- Untreated SCID results in frequent, severe infections, growth retardation and
- a short life span. Several causes and types of SCID have been identified.
-
- Symptoms
-
- Young infants with SCID usually have some protection against infection
- because they retain maternal antibodies during the first few months of life.
- After this period, however, infections become extremely frequent. Otitis
- media, pneumonia, sepsis, diarrhea, and skin infections recur constantly.
- The child becomes thin and weak, and growth slows drastically. Opportunistic
- organisms that may cause fatal infections include Candida albicans (a yeast
- that normally causes thrush and related infections), vaccinia, varicella
- (chickenpox), measles, cytomegalovirus, and the live bacteria in the BCG
- vaccine against tuberculosis. Pneumocystis carinii is a common cause of
- pneumonia that is very difficult to treat.
-
- SCID patients also do not reject foreign tissue. Immunocompetant cells
- introduced into the patient's body may cause graft-versus-host-disease,
- reacting primarily against the recipient's skin, liver, gut, and bone marrow.
- Such cells may derive from the administration of fresh whole blood containing
- incompatible lymphocytes, or unmatched bone marrow. The patients do not
- reject transplants which facilitates the transplantation of bone marrow, one
- of the only effective treatments in this disorder.
-
- Patients do not have cutaneous reactions to antigens, and they do not
- develop allergic reactions. After immunization, no antibodies are formed; if
- immunization is with a live vaccine, fatal infections may ensue.
-
- Many individuals with SCID related to adenosine deaminase deficiency have
- skeletal abnormalities, particularly of the rib cage.
-
- T- and B-lymphocytes in the blood of SCID patients are usually severely
- reduced in number or absent, as are serum immunoglobulins (antibodies). In
- some patients, individual immunoglobin classes may be present in normal or
- even elevated concentrations, and rarely, a patient may have low or normal
- numbers of B- and/or T-lymphocytes. None of these cells, or proteins,
- however, function properly. SCID patients have small, undeveloped thymuses,
- their lymph nodes are devoid of lymphocytes, and tonsils, adenoids, and other
- lymphoid organs are poorly developed or absent.
-
- In SCID with leukopenia, sometimes known as reticular dysgenesis,
- granular leukocytes are also absent or greatly reduced in number. The
- granulocytes are white blood cells which engulf invading microorganisms,
- especially bacteria. Patients with SCID with leukopenia have virtually no
- means of removing invading organisms from the body.
-
- Causes
-
- Hereditary SCID occurs in autosomal recessive and X linked recessive forms.
-
- 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.
-
- 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 have only 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.)
-
- Some cases of autosomal recessive SCID can be attributed to a deficiency
- of the enzyme adenosine deaminase (ADA). A lack of ADA results in high
- levels of adenosine in the plasma. Lymphocytes "trap" unusually high levels
- of this adenosine because they have an enzyme which converts it to
- deoxyadenosine triphosphate. This substance cannot leave the cell, and it
- affects the regulation of DNA synthesis. In this way, cell division, the
- production of antibodies, and other metabolic processes are severely
- disrupted. In the "bare lymphocyte" syndrome, clinical SCID is associated
- with a lack of histocompatibility antigens and B2 microglobin on the
- lymphocytes. Both of these proteins help distinguish cells belonging to the
- individual from foreign ones; in addition, it is thought that they are
- essential to the maturation of functional T-lymphocytes.
-
- Affected Population
-
- Severe Combined Immunodeficiency is estimated to occur with a frequency of
- about 1 in 100,000 to 500,000 live births.
-
- Related Disorders
-
- Various other forms of immunodeficiency exist. They include the acquired
- immune deficiency syndrome, isolated defects of T-cell function, and various
- antibody disorders.
-
- Therapies: Standard
-
- Bone marrow transplantation can cure this disorder if an identical match can
- be found to donate the marrow. Graft-versus-host (GVH) disease often occurs,
- and may be severe if the tissues are poorly matched. The use of haplo-
- identical bone marrow cells, treated to remove those cells likely to cause
- GVH disease, but leaving stem cells intact, has facilitated this procedure
- greatly. Fetal liver grafts, which contain lymphoid and white blood stem
- cells, have been effective in some cases in restoring T-cell function, but
- not in restoring the ability to produce antibodies. Fetal thymus grafts have
- usually been unsuccessful. In ADA deficiency, limited immunologic function
- may be restored by regularly transfusing red blood cells, which seem to be
- able to absorb and metabolize some of the excess circulating adenosine. Care
- must be taken to remove viable lymphocytes, as these could produce GVH
- disease. Iron overload is a possible side effect.
-
- In isolated cases, agents such as transfer factor, thymosin, and
- levamisole may augment existing cellular immunity.
-
- In 1990 the FDA approved PEG-ADA, an orphan drug that replaces the ADA
- enzyme deficiency in SCID. Children taking PEG-ADA through a weekly
- injection have had a normal immune system restored and they are recovering
- from infections that might previously have been deadly. For more information
- on PEG-ADA, please contact:
-
- Enzon Inc.
- 300C Corporate Court
- South Plainfield, NJ 07080
- (201) 668-1800
-
- Infections in people with SCID must be treated vigorously with
- antifungal, antibiotic, and supportive measures. P. carinii pneumonia can be
- particularly difficult to treat; the two drugs used are usually trimethoprim-
- sulfamethoxazole and the orphan drug pentamidine idethionate. (For further
- information on treatment, choose "AIDS" as your search term in the Rare
- Disease Database.) Cytomegalovirus and generalized herpes simplex infections
- are preferentially treated with idoxuridine, floxuridine, or cytabaradine.
- Severe candida and related fungii usually respond to amphotericin B therapy.
-
- Therapies: Investigational
-
- Scientists at Johns Hopkins University in Maryland are studying the use of
- thalidomide as a treatment for Graft vs. Host disease (GVHD). Preliminary
- studies indicate that it may have beneficial side effects on skin and hair
- symptoms. The major side effect of thalidomide is sedation, and it causes
- serious birth defects when given to pregnant women. More research is
- necessary to determine long-term safety and effectiveness of this treatment
- for GVHD. Thalidomide is available in England under special license from
- Penn Pharmaceuticals of Tredegar, South Wales.
-
- Scientists at the National Institutes of Health intend to try "gene
- therapy" on SCID patients with the hope of inserting a gene that manufactures
- ADA in these patients.
-
- The FDA Orphan Products Division awarded a grant in 1988 to Dr. Carol Michele
- Paradise, M.D., of Cetus Corporation, Emeryville, CA, for her treatment of
- Severe Combined Immunodeficiency with Interleukin-2.
-
- ADA deficient Severe Combined Immune Deficiency has been chosen as the
- first disease to be treated by "human gene therapy." The National Institutes
- of Health (NIH) are using the experimental procedure, in combination with the
- orphan drug PEG-ADA, to enhance the immune system of children with ADA
- deficient SCID. The procedure involves implanting a gene that makes human
- ADA into an activated virus. When the virus merges into the patient's cells,
- it manufactures the human enzyme. The corrected cells will be infused into
- the patient every few months. Patients interested in participating in this
- experimental protocol should ask their physicians to contact:
-
- Dr. Nelson Wivel
- Office of Recombinant DNA Activities
- National Institutes of Health, Bldg. 31, Rm. 4B11
- Bethesda, MD 20892
-
- Clinical trials are underway to study patients with genetically-
- determined immunodeficiency diseases. For infants with Severe Combined
- Immunodeficiency Disease (SCID), a highly effective new form of therapy is
- offered. Interested persons may contact:
-
- Rebecca H. Buckley, M.D.
- Box 2898
- Duke University Medical Center
- Durham, NC 27710
- (919) 684-2922
-
- to see if further patients are needed for this study.
-
- This disease entry is based upon medical information available through
- January 1992. 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 Severe Combined Immunodeficiency, please contact:
-
- National Organization for Rare Disorders (NORD)
- P.O. Box 8923
- New Fairfield, CT 06812-1783
- (203) 746-6518
-
- Immune Deficiency Foundation
- 3565 Ellicott Mill Drive, Unit B2
- Ellicott City, MD 21043
- (800) 296-4433
- (410) 461-3127
-
- Dr. M. Hershfield
- Duke University Hospital
- Room 418 Sands Bldg.
- Durham, NC 27710
-
- NIH/National Institute of Allergy and Infectious Diseases
- 9000 Rockville Pike
- Bethesda, MD 20892
- (301) 496-5717
-
- References
-
- Immunodeficiency. Buckley, R.H.; J Allergy Clin Immunol 1983 Dec; 72(6):627-
- 641.
-
- Metabolic Defects in Immunodeficiency Diseases. Webster, A.D.B.; Clin Exp
- Immunol 1982 Jul; 49(1):1-10.
-
- Combined Immunodeficiency and Thymic Abnormalities. Webster, A.D.B.; J
- Clin Pathol (Suppl) 1979; (13):10-14.
-
- MENDELIAN INHERITANCE IN MAN, 8th ed.: Victor A. MuKusick, Johns Hopkins
- University Press, 1986. Pp. 794, 18.
-
- THE METABOLIC BASIS OF INHERITED DISEASE, 5th Ed.: John B. Stanbury, et
- al.; eds; McGraw Hill, 1983. Pp. 2354.
-
-