Severe combined immunodeficiencies (SCID) are a type of primary immunodeficiency, which is a group of genetic conditions that affects the immune system’s ability to fight and protect the body from infections.¹ In SCID, the body’s immune cells (specifically T cells and including B cells and/or NK cells) are absent or not working properly, resulting in little or no immune response. This causes individuals with SCID to be highly susceptible to yeast, viral and bacteria infections, and can be life-threatening if left untreated.² SCID in children also results in failure to thrive, which is the difficulty to grow and gain weight as expected.³

SCID is caused by genetic defects in genes that affect these immune cells.⁴ There are a number of different genes that are affected in SCID with each gene causing a different SCID condition.

In Australia, SCID is often detected shortly after birth via newborn bloodspot screening (NBS) programs. For individuals who are not screened at birth, SCID is often diagnosed after symptoms develop. Early detection and diagnosis of SCID can ensure early interventions and prevent infections from being life-threatening to children with SCID.

Synonyms: SCID; Bubble boy syndrome; Combined t and b cell inborn immunodeficiency

Depending on the type of immune cells affected, SCID conditions may be described as one of the following:⁵

• T– B+ NK+ SCID
• T– B+ NK– SCID
• T– B– NK+ SCID
• T– B– NK– SCID

In a clinical context, SCID conditions may be described as the following depending on the clinical features of the condition:⁶

• leaky or atypical SCID
• typical or classic SCID
• variant SCID

Universal rare disease classifications provide a common language for recording, reporting and monitoring diseases. Please visit the Rare Disease Classifications page for more information about these internationally recognised classifications.

ORPHA:183660 Severe combined immunodeficiency

ICD-11: 4A01.10 Severe combined immunodeficiencies

Symptoms of SCID often present during the first few months of life but may not appear immediately after birth due to the presence of antibodies from the mother that are transferred during pregnancy and can protect the babies for the first few weeks or months.²

If SCID is not diagnosed early and treated, common symptoms of SCID often include:^2,3,5,6

• failure to thrive (difficulty growing and gaining weight as expected)
• delayed growth
• rashes
• thrush that keeps coming back (recurring) or that won’t go away (persistent)
• constant diarrhea
• repeated (recurrent) and severe infections – this could be fungal, bacteria, or viral infections.

Children with SCID are more susceptible to getting an infection and are unable to fight these infections unlike children with healthy immune systems.² Infections that may be mild or not as severe, or in some cases that do not cause any symptoms in healthy children often become life-threatening in children with SCID. If untreated, SCID can lead to early death.

There may be other symptoms as well depending on the type of SCID. SCID may also affect organs such as the brain, skull and central nervous system, inner ear and auditory nerve, as well as the liver.⁵

Please speak to your medical team to learn more about the symptoms and complications of this condition.

Rare diseases are often serious and progressive, exhibiting a high degree of symptom complexity, leading to significant disability. Majority of the estimated two million Australians living with a rare disease meet the Australian Government’s definition for disability (in accordance to the Australian Public Service Commission and Australian Bureau of Statistics), and many experience severe and permanent disability impacts. If you or someone you care for is experiencing disability-related impacts from a rare condition, please speak with a health or disability professional for advice. Information about relevant disability support can be found at the RARE Portal’s Disability Support Information page.

SCID is a genetic condition. It is caused by disease-causing genetic changes (variants) in genes that affect immune cells. Depending on the gene affected, this can cause a different type of SCID. There are over 18 different genes that can cause SCID, but in some cases the causal gene is unknown.⁴ Among the genes that can cause SCID are IL2RG, ADA, JAK3, IL7R, CORO1A, LAT, SLP76, CD3D, PTRPC, RAG1, RAG2, DCLRE1C, PRKDC, LIG4, NHEJ1, AK2, RAC2, CD247 and FOXN1. There may be other genes implicated in SCID that have not been listed here.

The disease-causing genetic variants can be inherited (passed down from parents to the next generation). Depending on the gene that is affected, a specific type of SCID may be inherited in an autosomal recessive or X-linked manner.

More information about inheritance patterns can be found at:

• Centre for Genetics Education: Autosomal recessive inheritance
• Centre for Genetics Education: X-linked inheritance

If you would like to learn more about the inheritance and impact of this condition, please ask your doctor for a referral to a genetic counsellor. Genetic counsellors are qualified allied health professionals who can provide information and support regarding genetic conditions and testing. More information about genetic counselling can be found at:

• Information on Genetic Services
• The National and State Services pages underneath the ‘Genetic Counselling’ sections listed

Newborn screening

In Australia, SCID is usually detected via the newborn bloodspot screening (NBS) programs.  Shortly after birth and with parental consent, a nurse or midwife will collect the baby’s blood via a heel prick blood test. The healthcare provider will then send it to a specific laboratory to test for a range of rare conditions, including SCID. If the results of these tests suggest that the baby is at risk of having one of these conditions, laboratory staff will quickly get in touch with healthcare providers. The healthcare providers will then arrange for the baby to have further testing that will confirm whether the baby does indeed have the condition. The healthcare providers will also organise for the baby to receive urgent care if required. 

Newborn bloodspot screening is a reliable way to check for certain rare conditions early in life. Although it’s extremely rare, cases can sometimes be missed. If you are concerned your baby may have a condition that they have already been screened for, you should contact a medical professional.  

SCID was progressively introduced into newborn bloodspot screening programs across Australia and as of 2024, is now included as part of routine newborn screening nationally.  Babies that were born prior to that may not have been screened for SCID. 

Diagnosis

A diagnosis of SCID may be suspected based on an abnormal result from NBS but additional tests and a clinical examination will be required to confirm a diagnosis. For individuals who are not screened at birth, SCID is often diagnosed after symptoms develop.

Diagnosis of SCID is typically made based on clinical examination, laboratory evaluations and genetic testing. Blood tests are performed to assess for decreased T-cell counts or T-cell receptor excision circles (TRECs), as well as to look at levels of immunoglobulins. Lymphocyte subset analysis, including assessment of B and NK cells levels, can determine which other immune cells are affected, and genetic testing is used to identify the causal defect of the condition.^5,6,7

As a part of the diagnosis, doctors may rule out other conditions that have similar symptoms, such as other types of primary and secondary immunodeficiencies including DiGeorge syndrome (22q11.2 deletion syndrome), CHARGE syndrome, congenital TORCH infection, X-linked or autosomal recessive agammaglobulinemia, and other forms of hypogammaglobulinemia.^2,5

Please speak to your medical team to learn more about the available pathways for diagnosis of this condition.

Survival outcomes for children with SCID has improved due to newborn screening leading to earlier diagnosis and advances in transplantation and supportive care. Many children who are treated early achieve good immune function and can have normal development, although some require ongoing specialist follow-up for immune function, infections, autoimmune complications, growth and other long-term health issues.

A treatment option for SCID is haematopoietic stem cell transplantation (HSCT).^7-9 HSCT involves the transplant of stem cells from the blood or bone marrow of a healthy donor into babies with SCID. The transplanted donor stem cells then produce functional immune cells that can fight infections and help protect individuals with SCID. Whilst HSCT can be curative, it carries risks and the procedure should be performed in a specialist centre with suitable expertise and facilities that can isolate and prevent babies with SCID from getting any infections before treatment.⁷ The effectiveness of HSCT as a treatment option for SCID depends on factors such as the availability of a suitable donor and when the procedure is performed, with better outcomes obtained when performed within the first 3-6 months of life and with no active infection.^2,4,8 Early diagnosis is therefore essential to enable timely intervention. It is also important to take measures to prevent individuals with SCID from getting infections, both before curative treatment and afterwards, whilst their immune system is rebuilding. This may involve staying in a sterile environment, limiting contact with others especially those who are sick and infection prophylaxis (medication or therapies to actively prevent infections).^7,9 There should also be regular screening for infections and immediate action to treat infections. Symptoms of SCID should also be addressed and managed, such as nutritional care for infants who have failure to thrive and persistent diarrhoea, management of rashes and skin issues, management of sensory and auditory issues, development delays, and other complications.

For individuals with adenosine deaminase deficiency (ADA-SCID), enzyme replacement therapy (ERT) may be available as a treatment option. In ADA-SCID, individuals are unable to produce the ADA enzyme. Enzyme replacement therapy for ADA-SCID involves regular injections of a purified enzyme to replace the missing enzyme in the body. While ERT can be effective in the short term, it does not correct the underlying genetic cause of the condition and is not a cure. It is often used as a short-term therapy whilst planning for curative treatment.⁷

Please speak to your medical team to learn more about the possible treatment or management options for your condition. Treatment will depend on an individual’s specific condition and symptoms. It is also important to stay connected to your medical team so that you can be made aware of any upcoming clinical trial opportunities. For many rare diseases, treatment options may be limited. Participation in a clinical trial may provide access to new or emerging therapies.

Healthcare professionals involved in the care of individuals with SCID may include general practitioners (GP), paediatricians, clinical immunologists, immunology nurses, dentists, dietitians, genetic counsellors, occupational therapists and physiotherapists. The need for different healthcare professionals may change over a person’s lifetime and extend beyond those listed here.

Clinical care for rare diseases often involves a multidisciplinary team of medical, care and support professionals. Please note that the information provided here is as a guide and that RVA does not necessarily monitor or endorse specific clinics or health experts.

This may not be applicable to all rare diseases but for many, palliative care services may be relevant and useful. Palliative care services are available for people (adults, children and their families) living with a life-limiting illness and is not only for end-of-life care. It can also help at any stage of illness from diagnosis onwards, and will look different for different people. Palliative care services provide assistance, support, resources and tools to help people manage their illness and the symptoms, ease pain, and improve comfort and quality of life. If this is relevant to you and you wish to find out more information about palliative care and how it can help you, please visit:

• Australian Institute of Health and Welfare: Palliative care Overview
• Australian Government Department of Health, Disability and Ageing: Palliative care
• Palliative Care Australia

Australasian Society of Clinical Immunology and Allergy (ASCIA): ASCIA-TAPID Consensus Guideline – Diagnosis, Management and Transplantation of SCID in Australia and New Zealand outlines the recommendations from the ASCIA Transplantation and Primary Immunodeficiency (TAPID) group and provides a proposed framework for the early investigation, management and supportive care prior to Haematopoietic Stem Cell Transplantation (HSCT), in the anticipation of introduction of routine newborn screening (NBS) for SCID in Australia. This guideline was developed by the ASCIA TAPID Group in collaboration with ANZCHOG, the Australian & New Zealand Children Haematology/Oncology Group in 2019.⁷

ASCIA Newborn Screening for Severe Combined Immune Deficiency (SCID) and BCG Vaccination Position Statement outlines recommendations based on expert experience and consensus; developed in 2024.

The following guidance is available from international experts outside Australia; however, there may be information that is not relevant or applicable to the Australian context, and may not be up to date:

• The diagnosis of severe combined immunodeficiency (SCID): The Primary Immune Deficiency Treatment Consortium (PIDTC) 2022 Definitions is a revision of the PIDTC 2014 Criteria for the diagnosis of SCID. The PIDTC is a part of the Rare Diseases Clinical Research Network (RDCRN), a key initiative of the Office of Rare Diseases Research (ORDR), part of the National Institutes of Health (NIH)’s National Center for Advancing Translational Sciences (NCATs) in the United States of America.⁶

Individuals living with rare diseases may have complex medical issues and disabilities, which are not always visible. It is often useful to refer to their medical history as well as personal information such as a medical card, doctor’s letter, or if available, a rare disease passport, for relevant information.

In addition, individuals, their parents, families and carers often develop extensive expertise on their specific rare disease. It is important to recognise that they can contribute valuable knowledge about their rare condition. Rare diseases often impact individuals differently, so it’s important to consider a person’s lived experience.

It may be important to consider the following when managing individuals living with SCID at emergency departments/services:

• prompt recognition and treatment of infections
• contacting an immunology specialist for suspected SCID cases or if there are any concerns about known cases

Australian Organisation:

Immune Deficiencies Foundation Australia (IDFA)
Website: https://www.idfa.org.au/

IDFA is a national not-for-profit and leading peak body offering education, advocacy and awareness for Australians living with primary or secondary immunodeficiencies.

Please note that RVA does not monitor or endorse each group/organisation’s operational governance and activities. When engaging with a group, please consider the information on the RARE Portal’s Finding Helpful Peer and Community Supports page.

SCID varies between individuals, and each person’s experience is unique.

Immune Deficiencies Foundation Australia: SCID Newborn Screening page has personal stories of people living with SCID.

If you would like to share your personal story with RVA, please visit the Rare Voices Australia: Share Your Story page. RVA will consider your story for publishing on our website and inclusion on the RARE Portal.

Immune Deficiencies Foundation Australia: SCID Newborn Screening has an online community for their members who are carers of a child with SCID.

For information on available government and social services that provide support for individuals with a rare disease, please visit the National and State Services pages.

People living with a rare disease often face unique challenges such as diagnostic delays, misdiagnoses, limited treatment options, and limited access to rare disease specialists and support. These challenges may impact people’s emotional wellbeing and quality of life. Many find it helpful to seek mental health and wellbeing support to cope with ongoing stress and uncertainty. Connecting with people who have shared experiences through a support group may also be helpful. Information about relevant mental health and wellbeing support can be found at:

• Mental Health and Wellbeing Support for Australians Living with a Rare Disease
• The National and State Services pages underneath the ‘Mental Health’ sections listed

Further information on SCID can be found at:

• Australasian Society of Clinical Immunology and Allergy (ASCIA): Information for Patients and Carers – Severe Combined Immunodeficiency (SCID) Frequently Asked Questions
• Genetic and Rare Diseases (GARD) Information Center: Severe combined immunodeficiency
• National Organization for Rare Disorders (NORD): Severe Combined Immunodeficiency

Orphanet: Severe combined immunodeficiency

Australasian Society of Clinical Immunology and Allergy (ASCIA): Resources for health professionals – Immunodeficiency and Autoimmunity

ASCIA Immunodeficiency Strategy for Australia and New Zealand

ASCIA Newborn Screening for Severe Combined Immune Deficiency (SCID) and BCG Vaccination Position Statement

ClinGen Clinical Genome Resource: Severe Combined Immunodeficiency Disease Variant Curation Expert Panel

Primary Immune Deficiency Treatment Consortium

This page has been co-developed by Rare Voices Australia (RVA)’s RARE Portal team in consultation with Immune Deficiencies Foundation Australia (IDFA).

If you are aware of any additional information that may benefit stakeholders with an interest in this page, or if you notice any broken links or inaccurate information, please let us know via the Contribute page.