Skip to
  1. Homepage
  2. Rare diseases
  3. Search
Simple search

Simple search

(*) mandatory field


Other search option(s)

Severe combined immunodeficiency due to adenosine deaminase deficiency

Synonym(s) ADA deficiency
SCID due to adenosine deaminase deficiency
Prevalence 1-9 / 1 000 000
Inheritance Autosomal recessive
Age of onset Infancy
  • D81.3
  • C0392607
  • C531816
  • 10066367


Disease definition

Severe combined immunodeficiency (SCID; see this term) due to adenosine deaminase (ADA) deficiency is a form of SCID characterized by profound lymphopenia and very low immunoglobulin levels of all isotypes resulting in severe and recurrent opportunistic infections.


SCID due to ADA deficiency accounts for 10-15% of all cases of SCID. Its annual incidence is estimated to be between 1/200,000 and 1/1,000,000 live births. Both males and females are affected.

Clinical description

SCID due to ADA deficiency has a variable clinical presentation. The most common form presents in infancy with severe and recurrent opportunistic infections (including respiratory tract infections and candidiasis), failure to thrive, and usually results in early death. Ten to 15% of patients have a delayed clinical onset by age 6-24 months, and a smaller percentage have a partial form of ADA deficiency with later onset between ages 4 years and adulthood, both types showing less severe infections and gradual immunologic deterioration. Patients may also present with extraimmune manifestations (including neurodevelopmental deficits, behavioral disorders, sensorineural deafness, and skeletal and hepatic abnormalities) as a result of the systemic nature of ADA expression.


SCID due to ADA deficiency is caused by mutations in the ADA gene (20q13.11). The extraimmune manifestations are caused by toxic levels of purine metabolites that result from the deficiency of ADA.

Diagnostic methods

Diagnosis is based on evidence of low or undetectable ADA activity in erythrocytes in combination with evidence of a marked reduction of T, B and NK cell counts when compared to age-matched healthy controls. Diagnosis can be confirmed by raised levels of dATP and reduced S-adenosyl homocysteine hydrolase (SAHH) activity in red cells and elevated amounts of deoxyadenosine in urine.

Differential diagnosis

Differential diagnosis includes all forms of SCID.

Antenatal diagnosis

Prenatal diagnosis can be carried out through mutation analysis or measurement of enzyme activity in trophoblasts cultured from chorionic villus sampling or in cultured amniocytes.

Genetic counseling

Transmission is autosomal recessive.

Management and treatment

Treatment is based on allogenic hematopoietic stem cell transplantation (HSCT), enzyme replacement therapy with pegylated adenosine deaminase enzyme or gene therapy by infusion of CD34+ marrow cells that have been transduced with an ADA-containing vector.


Prognosis depends on the severity of the disease. Without treatment, SCID due to ADA deficiency that presents in infancy usually results in early death. Survival rates after allogenic hematopoietic stem cell transplantation or gene therapy are high.

Expert reviewer(s)

  • Dr Andrew GENNERY

(*) Required fields.

Attention: Only comments seeking to improve the quality and accuracy of information on the Orphanet website are accepted. For all other comments, please send your remarks via contact us. Only comments written in English can be processed.

Captcha image

Detailed information

Article for general public
Clinical genetics review
Get Acrobat Reader
The documents contained in this web site are presented for information purposes only. The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment.