Severe combined immunodeficiency due to DNA-PKcs deficiency

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ORPHA:317425OMIM:615966D81.1
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Overview

Severe combined immunodeficiency due to DNA-PKcs deficiency (also called SCID due to PRKDC deficiency or DNA-PKcs SCID) is an extremely rare and life-threatening inherited immune disorder. It is caused by mutations in the PRKDC gene, which provides instructions for making an enzyme called DNA-dependent protein kinase catalytic subunit (DNA-PKcs). This enzyme plays a critical role in a process called V(D)J recombination, which is essential for the development of functional T cells and B cells — the white blood cells that fight infections. Without working DNA-PKcs, the body cannot produce these immune cells properly, leaving affected infants with virtually no immune defense against bacteria, viruses, and fungi. Babies with this condition typically appear healthy at birth but begin developing severe, recurrent, and life-threatening infections within the first few months of life. Common problems include persistent thrush (oral yeast infections), chronic diarrhea, pneumonia, skin infections, and failure to thrive. Because the immune system is so severely compromised, even common childhood illnesses like chickenpox or a cold can become fatal without treatment. This form of SCID is classified as a T-negative, B-negative SCID (T-B-SCID), meaning both T cells and B cells are absent or severely reduced, while natural killer (NK) cells may be present. Without treatment, affected children rarely survive beyond the first year or two of life. The primary curative treatment is hematopoietic stem cell transplantation (bone marrow transplant), ideally performed as early as possible. Gene therapy is an area of active research but is not yet standard for this specific form of SCID. Early diagnosis through newborn screening for SCID (using the TREC assay) has dramatically improved outcomes by allowing treatment before severe infections occur.

Also known as:

Key symptoms:

Severe and recurrent infections starting in early infancyPersistent oral thrush (white patches in the mouth)Chronic diarrheaFailure to gain weight and grow (failure to thrive)Pneumonia or other serious lung infectionsSkin rashes or infectionsEar infections that keep coming backInfections caused by organisms that don't usually affect healthy people (opportunistic infections)Absence or very low levels of T cells and B cellsInability to fight off common childhood illnessesSwollen lymph nodes may be absent due to lack of immune cellsSepsis (life-threatening bloodstream infection)

Inheritance

Autosomal recessive

Passed on when both parents carry the same gene change; often skips generations

Age of Onset

Neonatal

Begins at or shortly after birth (first 4 weeks)

Orphanet ↗OMIM ↗NORD ↗

Treatments

No FDA-approved treatments are currently listed for Severe combined immunodeficiency due to DNA-PKcs deficiency.

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No actively recruiting trials found for Severe combined immunodeficiency due to DNA-PKcs deficiency at this time.

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No specialists are currently listed for Severe combined immunodeficiency due to DNA-PKcs deficiency.

View NORD Rare Disease Centers ↗Undiagnosed Disease Network ↗

Treatment Centers

8 centers
🏥 NORD

Baylor College of Medicine Rare Disease Center

Baylor College of Medicine

📍 Houston, TX

🏥 NORD

Stanford Medicine Rare Disease Center

Stanford Medicine

📍 Stanford, CA

🔬 UDN

NIH Clinical Center Undiagnosed Diseases Program

National Institutes of Health

📍 Bethesda, MD

🔬 UDN

UCLA UDN Clinical Site

UCLA Health

📍 Los Angeles, CA

🔬 UDN

Baylor College of Medicine UDN Clinical Site

Baylor College of Medicine

📍 Houston, TX

🔬 UDN

Harvard/MGH UDN Clinical Site

Massachusetts General Hospital

📍 Boston, MA

🏥 NORD

Mayo Clinic Center for Individualized Medicine

Mayo Clinic

📍 Rochester, MN

👤 Mayo Clinic Center for Individualized Medicine

🏥 NORD

UCLA Rare Disease Day Program

UCLA Health

📍 Los Angeles, CA

Travel Grants

No travel grants are currently matched to Severe combined immunodeficiency due to DNA-PKcs deficiency.

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Community

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Caregiver Resources

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Social Security Disability

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Questions for your doctor

Bring these to your next appointment

  • Q1.How soon can my child receive a bone marrow transplant, and what type of donor is best?,What infection prevention measures should we follow at home right now?,Are there any vaccines my child or other family members should avoid?,What are the risks and expected outcomes of bone marrow transplant for this specific type of SCID?,Will my child need lifelong immunoglobulin replacement therapy, or could the transplant fully restore immune function?,Should our other children or future pregnancies be tested for this condition?,Are there any clinical trials or emerging therapies, such as gene therapy, that might be available for my child?

Common questions about Severe combined immunodeficiency due to DNA-PKcs deficiency

What is Severe combined immunodeficiency due to DNA-PKcs deficiency?

Severe combined immunodeficiency due to DNA-PKcs deficiency (also called SCID due to PRKDC deficiency or DNA-PKcs SCID) is an extremely rare and life-threatening inherited immune disorder. It is caused by mutations in the PRKDC gene, which provides instructions for making an enzyme called DNA-dependent protein kinase catalytic subunit (DNA-PKcs). This enzyme plays a critical role in a process called V(D)J recombination, which is essential for the development of functional T cells and B cells — the white blood cells that fight infections. Without working DNA-PKcs, the body cannot produce these

How is Severe combined immunodeficiency due to DNA-PKcs deficiency inherited?

Severe combined immunodeficiency due to DNA-PKcs deficiency follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.

At what age does Severe combined immunodeficiency due to DNA-PKcs deficiency typically begin?

Typical onset of Severe combined immunodeficiency due to DNA-PKcs deficiency is neonatal. Age of onset can vary across affected individuals.