Adenosine deaminase deficiency

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Adenosine deaminase (ADA) deficiency is a disorder that affects the immune system. Specifically, ADA deficiency impairs the development and function of immune cells called lymphocytes. Lymphocytes are white blood cells that help the body fight infections. As a result, people with ADA deficiency often develop pneumonia, chronic diarrhea, and widespread skin rashes. Additional signs and symptoms of ADA deficiency include slow growth and developmental delays.

About 80 percent of individuals with ADA deficiency also have severe combined immunodeficiency (SCID). People with SCID lack virtually all immune protection from bacteria, viruses, and fungi. They are prone to repeated and persistent infections that can be serious or life-threatening. These infections are often caused by "opportunistic" organisms that ordinarily do not cause illness in people with a normal immune system. People with ADA deficiency with SCID (ADA-SCID) typically develop health problems within the first 6 months of life. Without treatment, these babies usually do not survive past age 2.

About 15 to 20 percent of people with ADA deficiency develop health problems that begin between 1 and 10 years of age (delayed onset) or in adulthood (late onset). In people with this form of ADA deficiency (known as delayed or late-onset combined immunodeficiency or ADA-CID), the immune deficiency tends to be less severe than in people with ADA-SCID. People with ADA-CID typically have recurrent upper respiratory and ear infections. Over time, affected individuals may develop chronic lung damage, malnutrition, and other health problems.

In some individuals, ADA deficiency only impacts red blood cells. Since white blood cells are not affected, these individuals have normal immune systems. This form of the condition is known as partial ADA deficiency. Individuals with this form do not have any health problems related to the condition. They often only find out they have ADA deficiency when they undergo testing because of an affected relative or during a normal health screening.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Adenosine deaminase deficiency is caused by variants (also called mutations) in the ADA gene. This gene provides instructions for producing the enzyme adenosine deaminase. This enzyme is found throughout the body but is most active in lymphocytes. These cells protect the body against foreign invaders, such as bacteria and viruses. Lymphocytes are produced in specialized lymphoid tissues throughout the body, including in a gland located behind the breastbone called the thymus and in the lymph nodes.

The adenosine deaminase enzyme works to get rid of a molecule called deoxyadenosine, which is generated when DNA is broken down. A buildup of deoxyadenosine in cells can lead to early cell death. Adenosine deaminase converts deoxyadenosine to another molecule called deoxyinosine, which is not harmful. Variants in the ADA gene reduce or eliminate the activity of adenosine deaminase and allow deoxyadenosine to build up in cells. The severity of ADA deficiency generally depends on how much working enzyme is available. Individuals with ADA-SCID have no enzyme activity. Those with ADA-CID have greatly reduced enzyme activity, and people with partial ADA deficiency have somewhat reduced enzyme activity.

Immature lymphocytes in the thymus are particularly vulnerable to a toxic buildup of deoxyadenosine. These cells die before they can mature and help fight infection. The number of lymphocytes in other lymphoid tissues is also greatly reduced. The loss of infection-fighting cells results in the signs and symptoms of ADA deficiency.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a variant to cause the disorder. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Adenosine deaminase deficiency is very rare. It is estimated to occur in approximately 1 in 500,000 newborns worldwide. Approximately 15 percent of people with SCID have ADA deficiency.

Which doctor should you see?

The suggested department for discussing Adenosine deaminase deficiency is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

Where the source describes treatments, these are an overview of possible care, not a prescription for an individual. Ask which option applies to the confirmed diagnosis, what benefit is expected, what adverse effects to watch for and how progress will be assessed. Availability, approvals and local practice can differ from the country described in the source.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.