Decoding the Enigma of Partial Adenosine Deaminase Deficiency

Expert Reviewed By: ⁠Dr. Brandon Colby MD

Partial adenosine deaminase deficiency (pADA) is a rare genetic disorder that affects the immune system. It is a milder form of adenosine deaminase deficiency (ADA-SCID), which accounts for 15-20% of severe combined immunodeficiency (SCID) in humans. This article will discuss the genetic and biochemical aspects of pADA, its diagnosis, and the role of genetic testing in managing this disorder.

Understanding Partial Adenosine Deaminase Deficiency

pADA is caused by mutations in the ADA gene, which encodes the enzyme adenosine deaminase. This enzyme plays a crucial role in the breakdown of adenosine and other toxic molecules that can harm the immune system. When adenosine deaminase levels are low or absent, these toxic molecules accumulate and damage the immune system, making it difficult for the body to fight off infections and illnesses. The severity of the deficiency can range from mild to severe, with pADA representing a less severe form of the disorder.

Diagnosing Partial Adenosine Deaminase Deficiency

Diagnosing pADA can be challenging due to its rarity and the variety of symptoms it can cause. In some cases, individuals with pADA may experience recurrent infections, while others may have more severe symptoms such as neurological problems or inflammation of blood vessels (vasculitis). Early diagnosis is essential for proper management and treatment of the disorder.

Genetic Testing for pADA

Genetic testing is a powerful tool that can help identify the underlying cause of pADA. By analyzing the DNA sequence of the ADA gene, doctors can identify mutations that may be responsible for the deficiency. This information can be used to confirm a diagnosis of pADA and guide treatment decisions.

In one case report, genetic testing was used to diagnose a 3-year-old girl with a deficiency of adenosine deaminase 2 (DADA2) after she suffered a brainstem stroke. The early diagnosis allowed for appropriate treatment and management of her condition. In another case, genetic testing was used to identify a rare mutation in a 26-year-old male with a long-standing case of cutaneous polyarteritis nodosa, a form of vasculitis. The identification of the mutation led to a diagnosis of DADA2, which had caused recurring cutaneous ulcers and peripheral neuropathy.

Uses of Genetic Testing in pADA Management

Genetic testing can provide valuable information for the management of pADA. By identifying the specific mutation causing the deficiency, doctors can better understand the severity of the disorder and tailor treatment plans accordingly. Genetic testing can also be used to screen family members of affected individuals, allowing for early identification and intervention in at-risk relatives.

Treatment Options for Partial Adenosine Deaminase Deficiency

Treatment for pADA depends on the severity of the deficiency and the specific symptoms experienced by the individual. In some cases, enzyme replacement therapy (ERT) may be used to provide the body with functional adenosine deaminase, helping to reduce the accumulation of toxic molecules and improve immune function. In more severe cases, hematopoietic cell transplantation (HCT) may be considered. HCT involves the transplantation of healthy blood-forming cells from a donor to replace the damaged cells in the affected individual.

A recent study evaluating the outcomes of 131 ADA-SCID patients found that alternative donor HCT may be considered when matched sibling/family donor transplant and gene therapy are not available. This suggests that HCT may be a viable treatment option for some individuals with pADA who lack a suitable donor or are unable to undergo gene therapy.

Conclusion

Partial adenosine deaminase deficiency is a rare and complex genetic disorder that can have a significant impact on an individual’s immune system and overall health. Early diagnosis and appropriate treatment are crucial for managing the disorder and improving outcomes. Genetic testing plays a vital role in diagnosing pADA and guiding treatment decisions, making it an essential tool for healthcare providers and affected individuals alike.

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)