Adenosine deaminase 2 deficiency


Adenosine deaminase 2 deficiency is a vasculitis syndrome. It is due to mutations in the ADA2 gene which encodes the adenosine deaminase 2 protein. The clinical features of this condition are protean and it may be easily missed.

Signs and symptoms

The age of onset of symptoms is variable: 24% of reported patients present before 1 year of age. 77% present before the age 10 years. Adult onset has also been described. 5-10% die from this disease by the age of 30 years.
Like all vasculitis syndromes the features depend on which is organ is involved. Most commonly the gut, kidney and liver are affected. It may manifest as lacunar and/or hemorrhagic strokes, cutaneous lesions or polyarteritis nodosa. Hypertension and hepatosplenomegaly may occur.
It may affect the skin or brain. Polyarteritis nodosa in children is also known to occur.
Other conditions associated with this syndrome include hypogammaglobulinemia, pure red cell aplasia, immune thrombocytopenia and neutropenia.

Genetics

The ADA2 gene is located in the long arm of chromosome 22.
Over 60 pathogenic mutations have been recognised in ADA2. In all clinical cases to date both copies of the gene have been mutated implying a recessive inheritance.

Pathophysiology

This is not understood. The gene is expressed in myeloid cells and macrophages but its function is not known.

Diagnosis

Differential diagnosis

This includes common variable immunodeficiency, bone marrow failure and idiopathic aplastic anemia.

Treatment

, tumour necrosis factor antibodies and in severe cases bone marrow transplantation have been used successfully.

Epidemiology

This is a rare condition with less than 200 cases reported.

History

This condition was first reported in 2014.