Decoding the Mystery of SCID due to ADA Deficiency: Delayed Onset Unveiled

Expert Reviewed By: ⁠Dr. Brandon Colby MD

Severe combined immunodeficiency (SCID) is a group of rare genetic disorders characterized by a severely weakened immune system. One of the causes of SCID is adenosine deaminase (ADA) deficiency, which can lead to a delayed onset of the disease. In this article, we will explore the understanding, diagnosis, and the role of genetic testing in SCID due to ADA deficiency with delayed onset.

Understanding SCID due to ADA Deficiency: Delayed Onset

ADA deficiency is caused by mutations in the ADA gene, which is responsible for producing the adenosine deaminase enzyme. This enzyme plays a crucial role in the breakdown of toxic substances in the body, including adenosine and deoxyadenosine, which can be harmful to immune cells if not properly metabolized. When the ADA gene is mutated, the enzyme’s function is impaired, leading to a buildup of toxic substances and the subsequent destruction of immune cells, resulting in SCID.

While most cases of SCID due to ADA deficiency present in infancy, some individuals may experience a delayed onset of symptoms, which can occur later in childhood or even adulthood. This is often due to residual ADA enzyme activity, which may be sufficient to partially protect the immune system for a period of time. However, as the immune system continues to deteriorate, these individuals eventually develop the characteristic symptoms of SCID, such as recurrent infections, failure to thrive, and autoimmune disorders.

Diagnosing SCID due to ADA Deficiency: Delayed Onset

Diagnosing SCID due to ADA deficiency with delayed onset can be challenging, as the symptoms may be less severe and more variable than those seen in classic SCID. In addition to a thorough medical history and physical examination, several laboratory tests may be performed to aid in the diagnosis, including:

• Blood tests to assess immune cell counts and function
• Measurement of ADA enzyme activity in blood or other tissues
• Screening for the presence of toxic metabolites, such as adenosine and deoxyadenosine

In some cases, a diagnosis of SCID due to ADA deficiency may be suspected based on the presence of specific clinical features, such as cutaneous hypermelanosis, which has been reported as an early symptom in some individuals with the condition (1).

Genetic Testing for SCID due to ADA Deficiency: Delayed Onset

Genetic testing plays a vital role in confirming a diagnosis of SCID due to ADA deficiency, as well as in guiding treatment decisions and providing information for family planning. There are several ways in which genetic testing can be helpful for individuals with this disorder:

Identification of Disease-Causing Mutations

Genetic testing can be used to identify the specific ADA gene mutations responsible for an individual’s SCID due to ADA deficiency. This information can help clinicians and researchers better understand the genotype-phenotype correlations in this condition, potentially leading to improved treatment strategies (3).

Prenatal and Newborn Screening

For families with a known history of SCID due to ADA deficiency, prenatal genetic testing can be performed to determine if an unborn child is affected by the condition. In addition, newborn screening for SCID, which includes testing for ADA deficiency, is now available in many countries, allowing for early detection and intervention to improve outcomes for affected infants.

Carrier Testing and Family Planning

Individuals who are carriers of an ADA gene mutation may be at risk of having a child with SCID due to ADA deficiency. Genetic testing can help identify carriers within a family, providing valuable information for family planning and reproductive decision-making.

Guiding Treatment Decisions

Genetic testing can also be used to inform treatment decisions for individuals with SCID due to ADA deficiency. For example, the presence of specific ADA gene mutations may influence the choice of enzyme replacement therapy, gene therapy, or hematopoietic stem cell transplantation as potential treatment options.

In conclusion, understanding, diagnosing, and utilizing genetic testing for SCID due to ADA deficiency with delayed onset is crucial for improving the lives of affected individuals and their families. Advances in genetic testing technologies and increased awareness of this rare condition will continue to pave the way for better diagnostic and treatment options in the future.

About The Expert Reviewer

Dr. Brandon Colby MD is a US physician specializing in the personalized prevention of disease through the use of genomic technologies. He’s an expert in genetic testing, genetic analysis, and precision medicine. Dr. Colby is also the Founder of  and the author of ⁠⁠Outsmart Your Genes.

Dr. Colby holds an MD from the Mount Sinai School of Medicine, an MBA from Stanford University’s Graduate School of Business, and a degree in Genetics with Honors from the University of Michigan. He is an Affiliate Specialist of the American College of Medical Genetics and Genomics (⁠⁠ACMG), an Associate of the American College of Preventive Medicine (⁠⁠ACPM), and a member of the National Society of Genetic Counselors (⁠NSGC)