What is Adenosine Deaminase Deficiency?
Adenosine deaminase (ADA) deficiency, caused by harmful genetic changes (mutations) in the ADA gene, is a metabolic disease that affects lymphocytes, components of blood that play an important role in the immune system. ADA is an enzyme produced by the body that breaks down a toxic substance that results from natural processes in the cells. When there is a deficiency of ADA, the toxic substance builds up in the body and destroys lymphocytes. As a result, people with ADA deficiency can have higher risks for infections.
ADA deficiency is separated into different forms based on the age of onset and severity of symptoms.
ADA-Deficient Severe Combined Immunodeficiency Disease (ADA-SCID)
ADA-SCID is the most severe form of this condition and usually appears in the first six to twelve months of life. Infants may fall behind in growth (weight and height) and have a high chance of infection. Lung infections are common at this early age, and these and other infections can cause severe diarrhea, skin rashes, or other severe symptoms. Some individuals with ADA deficiency have skeletal (abnormal rib shape), liver, and neurological problems (cognition, behavior, and/or deafness).
Delayed/Late-Onset ADA Deficiency
About 15% of people with ADA deficiency first develop symptoms after six months of age. Usually symptoms will present within the first few years of life, but a small number of people do not have symptoms until their teens or adulthood. Effects of infections on individuals with delayed/late-onset ADA deficiency are usually less severe than those observed in people with ADA-SCID. These effects often include ear, nose, and throat infections and the appearance of warts on the hands and feet. Eventually, many develop chronic breathing problems and anemia.
Partial ADA Deficiency
Partial ADA deficiency does not typically result in symptoms or require treatment. Low levels of ADA enzymes that are present in this type function well enough to prevent symptoms. Thus, this form of the condition is generally recognized only by enzyme-based blood tests, though it may be predicted to some extent based on one's genetic test results.
How common is Adenosine Deaminase Deficiency?
The worldwide frequency of ADA deficiency in the general population has not been established. Where estimates have been made, the number of individuals affected with the condition each year ranges from 1 in 200,000 to 1 in 1,000,000 and the number of people affected with the condition each year in the US is approximately 1 in 600,000.
How is Adenosine Deaminase Deficiency treated?
Following a diagnosis of ADA deficiency, short-term treatment goals are focused on strengthening the immune system. This is often accomplished with various medications and infusions to help prevent or fight infections. The long-term treatment goal is to restore the function of the immune system through hematopoietic stem-cell transplant (HSCT). If a transplant is not possible or if the associated risks are too high, enzyme-replacement therapy is possible through intra-muscular injections. Researchers have also been experimenting with gene therapy for many years with some success. However, studies about long-term outcomes are still lacking.
What is the prognosis for an individual with Adenosine Deaminase Deficiency?
Without treatment, a child with ADA-SCID can die in the first two years of life. When treated with a transplant from a matched sibling or family member, up to 90% will survive for at least one year, with potentially higher success rates if this treatment is done within the first few months of life. Some have been found to restore immune systems even 10 years after transplant. The survival rate for transplants from unrelated donors is lower (up to 70%). There appears to be a higher chance of cognitive and behavioral abnormalities, in addition to hearing loss, associated with HSCT. When treated with enzyme-replacement therapy, the survival rates are similar to those for individuals who received transplants from an unrelated individual, but some have lived 8 to 10 years or more. Gene therapy, though still in the experimental stages, appears to be a promising option.