Introduction:
The birth of a healthy baby in a family is a wonderful miracle of life! The world is lit up by the extraordinary energy contained in the baby's tiny body. This moment is very precious and dreamlike in the lives of parents and family. The sweet smiling face of the baby inspires dreams of his bright future, but sometimes if the newborn has some birth defects or some diseases, this joy is literally ruined.
With the latest medical technology and diagnostic methods, many congenital diseases can be diagnosed while the baby is still in the womb, but some diseases are only noticed after the baby is born. One of the important diseases are inborn errors of immunity. Although these diseases are rare, their effects on the baby's health are very serious, so let's learn about these diseases.
What is immunity?
In our daily life, we encounter many microorganisms, including bacteria, viruses, fungi, and parasites like malaria. The system in the body to fight against such diseases is our immune system. This system includes certain whie blood cells, bone marrow, spleen, tonsils, thymus gland, etc.
Inborn Errors of Immunity (IEI), previously known as primary immunodeficiencies (PIDs), are a group of inherited disorders that weaken the immune system. This makes affected individuals more vulnerable to infections, autoimmune diseases, and even cancers. Although rare, these conditions are often underdiagnosed due to a lack of awareness. By understanding IEI, pediatricians and the general public can play a crucial role in early recognition and timely intervention, improving patient outcomes.
Why Should Pediatricians and the Public Be Aware?
IEI can present in early childhood to even adulthood with recurrent infections, unusual infections, refractory or multiple autoimmunity & recurrent or early cancers. Delayed diagnosis can lead to life-threatening complications, making early recognition essential.
Increased awareness can help in:
Prompt referral to an immunologist
Early initiation of life-saving treatments
Reducing complications and improving quality of life
What Are Inborn Errors of Immunity?
IEI are genetic disorders that impair the function of the immune system. More than 500 types have been identified, affecting different parts of the immune system.
These disorders can be classified into the following categories:
Combined Immunodeficiencies (CIDs) – Affect both T and B cells, such as Severe Combined Immunodeficiency (SCID), which is fatal if untreated.
Predominantly Antibody Deficiencies – Affect the body's ability to produce antibodies, such as X-linked Agammaglobulinemia,
Common Variable Immunodeficiency (CVID), leading to frequent respiratory infections.
Diseases of Immune Dysregulation – Conditions where the immune system attacks the body’s own tissues, such as Autoimmune Lymphoproliferative Syndrome (ALPS).
Phagocyte Defects – Affect white blood cells that destroy bacteria, such as Chronic Granulomatous Disease (CGD), causing persistent infections.
Innate Immunity Defects – Affect early immune responses leading to severe bacterial infections.
Autoinflammatory Disorders – Cause excessive inflammation without infection, such as Familial Mediterranean Fever (FMF), leading to recurrent fevers and joint pain.
Complement Deficiencies – Affect proteins that help fight infections, increasing susceptibility to bacterial infections.
How Do These Disorders Present?
The symptoms of IEI can vary widely, but some common warning signs include:
Frequent, severe infections – Ear, lung, or skin or gastrointestinal infections that require multiple antibiotic treatments.
Autoimmune symptoms – Unexplained fevers, rashes, or chronic diarrhea, severe and early onset endocrinopathy, severe atopic diseases.
Delayed growth and development – Failure to thrive in young children.
Family history of immune disorders – Increased risk if a sibling or parent has IEI.
When to Suspect IEI?
IEI should be suspected in any child with the following clinical features.
These are the Jeffrey Modell Foundations’
10 warning signs of primary immune deficiency. Presence of 2 or more of the following should raise the suspicion of PID:
1. ≥ 4 new ear infections within 1 year
2. ≥ 2 serious sinus infections within 1 year
3. ≥ 2 months on antibiotics with little effect
4. ≥ 2 pneumonias within 1 year
5. Failure of an infant to gain weight or grow normally
6. Recurrent, deep skin or organ abscesses
7. Persistent thrush in mouth or fungal infection on skin
8. Need for IV antibiotics to clear infections
9. ≥ 2 deep-seated infections including septicemia
10. A family history of PID
If any of these signs are present, an immunology referral should be considered.
In addition the age of onset can give a clue:
Age of onset noted before age 6 months suggests a T-cell defect or phagocytic defect.
Age between 6 and 12 months may suggest combined B- and T-cell defects or a B-cell defect as maternal antibodies wane out.
Onset later than 12 months usually suggests a B-cell defect or other combined B- and T-cell immunodeficiency.
How Are These Conditions Diagnosed?
IEI is diagnosed through a combination of:
Medical History and Physical Examination – Identifying recurrent infections, unusual pathogens, or family history.
Basic Blood Tests – Measuring white blood cells, immunoglobulins (antibodies), and lymphocyte counts (any infant with a lymphocyte count persistently below 3000-4000 cells/cumm especially in the presence of infections &/or failure to thrive should be evaluated further)
Advanced Immune Function Tests – Evaluating how the immune system responds to infections.
Genetic Testing – Identifying specific gene mutations responsible for IEI.
Treatment and Management
Although IEI is a lifelong condition, advances in medicine have made it manageable.
Treatments include:
Antibiotics and Antifungals – To prevent and treat infections.
Immunoglobulin Therapy (IVIG/SCIG) – Provides missing antibodies for antibody deficiencies.
Stem Cell Transplantation (HSCT) – Can cure severe IEI, such as SCID, by replacing defective immune cells. Currently many centres in India offer transplant facilities to children with IEI.
Gene Therapy – A promising approach for specific conditions like ADA-SCID.
Targeted Medications – Monoclonal antibodies and JAK inhibitors help regulate immune dysfunction.
Supportive Care – Proper nutrition, hygiene, and vaccinations (only non-live vaccines) are crucial.
Role of Pediatricians in Early Detection
Pediatricians are the first point of contact for children with recurrent infections.
They should :
Recognize warning signs of IEI.
Educate parents about early symptoms and risk factors.
Refer suspected cases to an immunologist for further evaluation.
Ensure timely immunization while avoiding live vaccines in children with suspected IEI.
How Can the Public Help?
Awareness among parents and caregivers is key to early diagnosis. Parents should:
Keep track of their child's infections and growth milestones.
Seek medical advice if infections seem frequent or severe.
Be aware of family history and genetic risk factors.
Advocate for genetic testing and expert consultations if needed.
How is the Government helping?
National Rare Disease Registry Program
Many IEI are included in India's National Policy for Rare Diseases, 2021. The government has designated 12 institutions as Centers of Excellence (CoEs) for rare diseases, actively managing patients and contributing to the National Rare Disease Registry (rarediseases.mohfw.gov.in) This initiative aims to promote research and development in the field of rare diseases, facilitating better diagnosis and treatment options. (rdrdb.icmr.org.in)
Leading referral centres in India for IEI
Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh
SGPGI Regional Diagnostic Center for Primary Immunodeficiencies at Lucknow
Bai Jerbai Wadia Hospital for Children, Mumbai
Regional Diagnostic and treatment Center for Primary Immunodeficiencies at Aster CMI Hospital, Bangaluru
NIMS Regional Diagnostic Center for Primary immunodeficiencies at Nizam Institute of Medical Science
Regional Diagnostic Center for primary immunodeficiencies at JIPMER, Puducherry
Conclusion
Inborn Errors of Immunity are often overlooked, leading to delayed diagnosis and complications. Increased awareness among pediatricians and the general public can significantly improve early detection and treatment outcomes. Recognizing the warning signs, seeking timely medical advice, and advocating for better diagnostic tools can save lives. With advances in medicine, many IEI patients now have access to effective treatments and an improved quality of life. By working together, healthcare professionals and families can ensure that no child with IEI is left undiagnosed or untreated.
Dr Vaishnavi Iyengar,
Consultant Immunology at BJWHC and SRCC hospital Mumbai
