| P A T T E R N S O F I N H E R I T A N C E |
Scientists studying inherited diseases group them according to the way in which the disease-causing gene is passed on. In general, "recessive" diseases occur when there is no normal copy of a gene to compensate for a defective one, while "dominant" diseases are manifest even with one normal and one abnormal gene copy. Diseases caused by defects in a single gene fall into one of the following categories: - X-linked recessive diseases are caused by genes located on the X chromosome. Although we have two copies of most genes, men have only one X chromosome and only one copy of genes on that X chromosome. If a man inherits a disease-causing gene mutation that is on the X chromosome, he has no backup normal X gene, and he will likely develop the disease.
A woman will not usually develop an X-linked recessive disease because she has two X chromosomes, but she can be a "carrier." She remains healthy because the normal gene on one X chromosome continues to function, even though she carries the mutated gene, and can pass it on to her children. With each and every pregnancy, there is an equal chance that the baby will be a boy with the disease, a healthy girl who is a carrier, a healthy boy, or a healthy girl who is not a carrier. | For some X-linked recessive immunodeficiency diseases, carriers can be identified by laboratory tests. With others, a woman is discovered to be a carrier only after she gives birth to a child with the disease. - Autosomal recessive diseases occur when a person inherits two faulty recessive genes located on autosomes (non-sex chromosomes), one from each parent; both parents are healthy carriers. These diseases are as likely to affect girls as boys. With every pregnancy, there is one chance in four that the baby will have the disease, two chances in four that the baby will be healthy but a carrier, and one chance in four that the child will be healthy and not carry a defective copy of the gene.
- Autosomal dominant disorders are caused by a single dominant gene. One of the parents is not just a carrier, but has the disease. Each child in the family has a 50-50 chance of inheriting the defective gene and the disorder.
- New mutations may cause diseases. In some cases, neither parent has the disease-causing mutation. This may occur because the mutation in the gene occurred in the parents’ germ cells (sperm or egg) but not other cells of their body. New mutations account for a substantial proportion (up to one-third) of X-linked immunodeficiency diseases.
| Although many PI diseases can be traced to a single gene, others cannot. No family pattern is evident, and they are said to occur "sporadically."
A sporadic disorder might be the result of several disabled genes interacting, interactions between particular forms of genes, and environmental influences. It might develop from gene changes that occur during a person’s lifetime. Or it might be due to new mutations in germ cells or an inheritance pattern that has not been recognized yet.
Some PIs are X-linked, others autosomal recessive. At least one is autosomal dominant. Some PIs have more than one pattern of inheritance. For example, a group of diseases known as Common Variable Immunodeficiency (CVID) can be inherited as autosomal recessive, autosomal dominant, or X-linked. Most cases of CVID, however, are sporadic. |
Besides all the infections, some immunodeficiency diseases produce other immune system problems, including autoimmune disorders. Autoimmune disorders develop when the immune system gets out of control and mistakenly attacks the body’s own organs and tissues.
In some autoimmune disorders, the faulty immune system targets a single type of cell or tissue. For example, an immune attack on blood cells can lead to anemia (a debilitating loss of red blood cells). An attack on islet cells of the pancreas can lead to diabetes (a disorder caused by insufficient amounts of insulin, a pancreatic hormone that helps the body convert digested food into energy).
In other situations, the immune system strikes multiple cells and tissues, producing diseases such as rheumatoid arthritis or systemic lupus erythematosus (SLE). Rheumatoid arthritis targets primarily the joints, but it can also damage nerves, lungs, and skin. Lupus strikes skin, muscles, joints, kidneys, and other organs, causing rashes, joint pain, fatigue, and fever, among other things.
Finally, an immunodeficiency can be just one part of a complex syndrome, with a telltale combination of signs and symptoms. For example, children with DiGeorge Anomaly not only have an underdeveloped thymus gland (and a corresponding lack of T cells), they typically have congenital heart disease, malfunctioning, or underdeveloped parathyroid glands, and characteristic facial features. Young boys with Wiskott-Aldrich Syndrome, in addition to being prone to infections, develop bleeding problems and a skin rash.
T H E 1 0 W A R N I N G
S I G N S O F P R I M A R Y
I M M U N O D E F I C I E N C Y * - Eight or more new ear infections within a year.
- Two or more serious sinus infections within a year.
- Two or more months on antibiotics with little effect.
- Two or more pneumonias within a year.
- Failure of an infant to gain weight or grow normally.
- Recurrent deep abscesses in the skin or organs.
- Persistent thrush in mouth or on skin, after age one.
- Need for intravenous antibiotics to clear infections.
- Two or more deep-seated infections such as meningitis, osteomyelitis, cellulitis, or sepsis.
- A family history of primary immunodeficiency.
*Courtesy of The Jeffrey Modell Foundation and the American Red Cross. |
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D I A G N O S I N G P I
Sometimes the signs and symptoms of a PI are so severe, or so characteristic, that the diagnosis is obvious. In most cases, it is not clear if a long string of illnesses are just "ordinary" infections, or if they are the result of an immunodeficiency.
Many conditions can produce an immunodeficiency, at least temporarily, and most children who seem to have "too many" infections are not, in fact, suffering from an immunodeficiency. Experts estimate that half of the children who see a doctor for frequent infections are normal. Another 30 percent may have allergies, and 10 percent have some other type of serious disorder. Just 10 percent turn out to have a primary or secondary immunodeficiency.
T H E B A S I C S
When a pattern of frequent infections suggests an immunodeficiency, the doctor begins by exploring the patient’s "history" and the family’s history, and then conducts a physical examination.
- The patient’s history. What infections has the patient had in the past, or has now? Have they been unusually frequent, or severe, or long-lasting? Have they failed to respond to standard treatments? When a child who is immunologically normal develops a string of infections, they are usually mild and short-lived, and between infections the child recovers completely.
