Table 1 Main features of DADA2 syndrome
From: A wide spectrum of phenotype of deficiency of deaminase 2 (DADA2): a systematic literature review
Genetic features | Mutation in ADA2: homozygous mutation or compound heterozygous or Heterozygosity |
Age at onset | Widely variable Mean 92.1Â months (Standard deviation 108.2) |
Costitutional symptoms | Recurrent fever: not specific pattern Failure to thrive Recurrent infections |
Mucocutaneous | Livedo reticularis Livedo racemose Erythema nodosum Urticarial rash Cutaneous vasculitis Leucocitoclastic vasculitis Panarteritis nodosa Skin ulcers Mouth and genital ulcers Eczema Raynaud Panniculitis Digital necrosis |
Neurologic | Stroke: ischaemic and haemorrhagic Demyelinating disease Polyneuropathy, cranial neuropathy (mono/polyneuropathy) Developmental delay |
Haematologic features | Anaemia (microcitic or pure red aplasia, or blackfan diamond anemia) Thrombocytopenia Lymphopenia Neutropenia Pancytopenia Hepatosplenomegaly Lymphoproliferation Lymphoma HLH |
Immunological features | Predominantly humoral immunodeficiency Low B cell Low B cell switched Pan-hypogammaglobulinemia Variable NK and T cell level Increased level of Double Negative lymphocytes Interferon signature: activation of the type I IFN pathway |
Lympho/splee | Splenomegaly Diffuse lymphadenopathies |
Gastrointestinal | Recurrent abdominal pain with diarrhoea and vomiting Bowel ischemia/perforation/necrosis Hepatic hyper-transaminasemia Hepatomegaly |
Renal | Vascular damage Haematuria |
Vessel | Vasculitis: panarteritis nodosa like with the development of aneurism |
Ophtalmologic | Uveitis Neuritis optica Periorbital inflammation Ocular vasculitis Papilledema Optic nerve atrophy |
Musculoskeletal | Arthralgia/arthritis Myopathies |
Others | Testicular involvement Recurrent warts |
Treatment | IVIG and subcutaneous IG replacement → Supporting therapy Anti-TNFα → good response. (possible bridge to HSCT) HSCT → resolution of vasculitis and immunodeficiency |