Adenosine deaminase deficiency

Adenosine deaminase deficiency
Classification and external resources
ICD-10 D81.3
ICD-9 279.2
OMIM 102700
DiseasesDB 260

Adenosine deaminase deficiency, also called ADA deficiency or ADA-SCID,[1] is an autosomal recessive[2] metabolic disorder that causes immunodeficiency. It occurs in fewer than one in 100,000 live births worldwide.

It accounts for about 15% of all cases of severe combined immunodeficiency (SCID).[3]

ADA deficiency may be present in infancy, childhood, adolescense, or adulthood.[1] Age of onset and severity is related to some 29 known genotypes associated with the disorder.[4]

Contents

Pathophysiology

ADA deficiency is due to a lack of the enzyme adenosine deaminase. This deficiency results in an accumulation of deoxyadenosine,[5] which, in turn, leads to:

Because T cells undergo proliferation and development in the thymus, affected individuals typically have a small, underdeveloped thymus.[6] As a result, the immune system is severely compromised or completely lacking.

Genetics

The enzyme adenosine deaminase is encoded by a gene on chromosome 20. ADA deficiency is inherited in an autosomal recessive manner.[1] This means the defective gene responsible for the disorder is located on an autosome (chromosome 20 is an autosome), and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.

Treatment

Treatments include:

On September 14, 1990,the first gene therapy to combat this disease was performed by Dr. W. French Anderson on a four year old girl, Ashanti DeSilva, at the National Institutes of Health, Bethesda, Maryland, U.S.A.[7]

References

  1. ^ a b c Online 'Mendelian Inheritance in Man' (OMIM) 102700
  2. ^ Hirschhorn R, Vawter GF, Kirkpatrick JA Jr., Rosen FS (September 1979). "Adenosine deaminase deficiency: frequency and comparative pathology in autosomally recessive severe combined immunodeficiency". Clinical immunology and immunopathology 14 (1): 107–20. doi:10.1016/0090-1229(79)90131-4. PMID 477037. 
  3. ^ Hershfield MS (October 2003). "Genotype is an important determinant of phenotype in adenosine deaminase deficiency". Current opinion in immunology 15 (5): 571–7. doi:10.1016/S0952-7915(03)00104-3. PMID 14499267. 
  4. ^ Arredondo-Vega FX, Santisteban I, Daniels S, Toutain S, Hershfield MS (October 1998). "Adenosine deaminase deficiency: genotype-phenotype correlations based on expressed activity of 29 mutant alleles". American journal of human genetics 63 (4): 1049–59. doi:10.1086/302054. PMC 1377486. PMID 9758612. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1377486. 
  5. ^ "Adenosine Deaminase (ADA) Deficiency". http://learn.genetics.utah.edu/units/disorders/whataregd/ada/. Retrieved 2008-02-28. 
  6. ^ p347, The Immune System Peter Parham, Garland Science, London and New York, 2009
  7. ^ Naam, Ramez (2005-07-03). "'More Than Human' - New York Times". The New York Times. http://www.nytimes.com/2005/07/03/books/chapters/0703-1st-naam.html. Retrieved 2008-02-28. 

External links