[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Conditions](https://durgical.com/en/conditions/) › Adenosine deaminase deficiency (ADA-SCID)

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# Adenosine deaminase deficiency (ADA-SCID)

An inherited disease in which a purine toxin kills lymphocytes; the baby is left without defences and gets severe infections.

Updated 2026-11-01

## Structures involved

Tap one to see what it is and open it in 3D.

- [Thymus](https://durgical.com/en/anatomy/thymus/)
- [Mediastinal lymph nodes](https://durgical.com/en/anatomy/mediastinal-lymph-nodes/)
- [Right lower lobe](https://durgical.com/en/anatomy/inferior-lobe-of-right-lung/)
- [Left lower lobe](https://durgical.com/en/anatomy/inferior-lobe-of-left-lung/)
- [Costal cartilages](https://durgical.com/en/anatomy/costal-cartilage/)

## In biochemistry

- [Pyrimidine synthesis: Step 8 · Ribonucleotide reductase](https://durgical.com/en/biochemistry/pathways/pyrimidine-synthesis/#paso-8)
- [JAK–STAT pathway](https://durgical.com/en/biochemistry/topics/jak-stat-pathway/)
- [Gene therapy](https://durgical.com/en/biochemistry/topics/gene-therapy/)
- [Adenosine deaminase (ADA)](https://durgical.com/en/biochemistry/enzymes/adenosine-deaminase/)
- [Ribonucleotide reductase](https://durgical.com/en/biochemistry/enzymes/ribonucleotide-reductase/)
- [Immunoglobulins (antibodies)](https://durgical.com/en/biochemistry/enzymes/immunoglobulins/)

## In immunology

- [V(D)J recombination: how a few genes make billions of receptors](https://durgical.com/en/immunology/v-j-recombination-how-a-few-genes-make-billions-of-receptors/)
- [Immunodeficiency: warning signs and the infection pattern by defect](https://durgical.com/en/immunology/immunodeficiency-warning-signs-and-the-infection-pattern-by-defect/)
- [T-cell and combined deficiencies: DiGeorge, SCID, Wiskott–Aldrich, ataxia-telangiectasia](https://durgical.com/en/immunology/t-cell-and-combined-deficiencies-digeorge-scid-wiskott-aldrich-ataxia-telangiect/)
- [T-cell development: positive and negative selection](https://durgical.com/en/immunology/t-cell-development-positive-and-negative-selection/)

## What it is

Autosomal recessive adenosine deaminase deficiency causing severe combined immunodeficiency (no T, B or NK cells) and damage to other organs.

## Who gets it

About 1 in 500,000 newborns; it accounts for about 15% of SCID. In Latin America newborn SCID screening (TREC) is not yet routine in most countries, so many cases are recognised late, sometimes after complications of the BCG vaccine given at birth.

## Causes

- Pathogenic variants in both copies of the ADA gene (autosomal recessive inheritance)

## Risk factors

- Carrier parents, consanguinity
- An affected sibling or a sibling's early death from infection

## Pathophysiology

Without ADA, adenosine and deoxyadenosine accumulate. Lymphocytes phosphorylate deoxyadenosine to dATP, which shuts down ribonucleotide reductase: without deoxynucleotides they cannot replicate DNA and die by apoptosis. Deoxyadenosine also inhibits S-adenosylhomocysteine hydrolase. The metabolic damage reaches other tissues (lung, bone, ear, brain and [liver](https://durgical.com/en/anatomy/liver/)).

## Classification

- Early-onset form (classic SCID, most cases)
- Delayed or adult-onset forms, with residual activity

## Symptoms and signs

- Severe, repeated infections from the first months (pneumonia, otitis, sepsis)
- Chronic diarrhoea and failure to thrive
- Persistent oral thrush
- Opportunistic infections such as Pneumocystis pneumonia
- Bone changes (flared costochondral junctions), sensorineural deafness and neurological or behavioural problems

## Red flags

- Breathing difficulty or hypoxaemia in an infant with repeated infections
- Persistent ulcer or axillary node after BCG (disseminated BCG)
- Marked lymphopenia on an infant's blood count
- Diarrhoea with dehydration and weight loss

## Diagnosis

**Clinical**
An infant with severe or opportunistic infections, diarrhoea and failure to thrive, with family history or consanguinity.

**Tests**
Profound lymphopenia (T-, B-, NK-) on flow cytometry; low immunoglobulins; very low red cell ADA activity and high deoxyadenosine nucleotides (dAXP); ADA genetic testing; low TRECs on newborn screening where available.

**Imaging**
[Chest](https://durgical.com/en/anatomy/region/chest/) X-ray shows an absent thymic shadow, pneumonias and flared anterior rib ends.

## Treatment

**Acute**
Protective isolation and intensive treatment of infections

**Medical**
Intravenous immunoglobulin and Pneumocystis prophylaxis

**Medical**
Enzyme replacement therapy with polyethylene glycol-conjugated ADA while definitive treatment is prepared

**Procedure**
Haematopoietic stem cell transplant, ideally from a matched sibling

**Procedure**
Gene therapy with the patient's own stem cells in specialised centres

**Follow-up**
Avoid live vaccines (including BCG) and use irradiated blood products

## Complications

- Disseminated infection from BCG or live vaccine viruses
- Chronic lung damage
- Deafness and cognitive deficits even after transplant
- Graft-versus-host disease after transplant

## Prognosis

Untreated, it is usually fatal within the first two years; with early transplant, enzyme or gene therapy, survival is high.

## Prevention

- Newborn TREC screening and family genetic counselling
- Delay BCG in newborns with a family history of SCID until it is ruled out

## Test yourself

Think of the answer, then tap the question to see it.

## Which toxic metabolite kills lymphocytes in ADA deficiency?

dATP, made from accumulated deoxyadenosine, which inhibits ribonucleotide reductase.

## Which chest X-ray finding suggests SCID in an infant?

Absence of the thymic shadow.

## Why is BCG a concern in a newborn with SCID?

It is a live bacterial vaccine: without T cells it can disseminate and cause severe disease.

## Which treatments can cure or control ADA-SCID?

Haematopoietic stem cell transplant, autologous gene therapy and, as a bridge, PEG-ADA enzyme replacement.

[Add to my cards (4)](https://durgical.app/estudiar/?add=/en/conditions/adenosine-deaminase-deficiency/)

## Related conditions

- [Community-acquired pneumonia](https://durgical.com/en/conditions/community-acquired-pneumonia/)
- [Tuberculosis](https://durgical.com/en/conditions/tuberculosis/)

Educational information, not medical advice. For any symptom, see a health professional.

Sources: [Adenosine deaminase deficiency: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/adenosine-deaminase-deficiency/) (MedlinePlus, US National Library of Medicine, 2026); [ADA gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/ada/) (MedlinePlus, US National Library of Medicine, 2026); [ADA: Adenosine deaminase (human)](https://www.uniprot.org/uniprotkb/P00813/entry) (UniProt, 2026).

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Source: https://durgical.com/en/conditions/adenosine-deaminase-deficiency/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/conditions/adenosine-deaminase-deficiency/