The signs and symptoms of disease are wide-ranging in severity, but can be grouped into vascular, immunologic, and hematologic manifestations. Individual patients typically present with disease of only one of these subtypes, but this is not always the case. Symptoms have also been known to abate and recur even without treatment. Twenty-four percent of patients have disease onset before 1 year of age, and 77% of patients have disease onset before 10 years of age. Vasculopathy is the hallmark of DADA2, and was the most prominent feature of the disease upon its initial discovery. The vasculitis seen in DADA2 is similar to polyarteritis nodosa (PAN), often leading to misdiagnosis. However, DADA2 patients typically have earlier disease onset, and a greater prevalence of skin and neurologic manifestations. The systemic inflammation present in DADA2 leads to this vasculopathy, with symptoms involving but not limited to skin, brain, gastrointestinal tract, and kidneys. Livedo racemosa and livedo reticularis are the most common manifestations in skin, although other symptoms such as digital necrosis, subcutaneous nodules, and non-specific rash have been seen. The most common neurological manifestations of DADA2 are secondary to vasculitis. Fifty-one percent of patients present with neurologic disease, typically in the form of lacunar stroke. In some patients, stroke can be the first indication of disease. Approximately 50% of patients have some form of immunologic or hematologic disease. While patients with vascular-predominant disease typically have only mild deficiencies in these areas, most DADA2 patients display deficiencies in IgG and IgM antibody production as well as overall poor B cell function. Bone marrow failure, pure red cell aplasia (PRCA), or immunodeficiency are the most serious manifestations in those who don't display the classic vascular disease. Those with the bone marrow failure phenotype commonly have hepatosplenomegaly, recurrent infection, and various cytopenias. Meanwhile, those with PRCA can display a similar disease to Diamond-Blackfan anemia. The onset of PRCA caused by DADA2 is commonly before one year of age, while children with bone marrow failure typically onset around two years of age. In patients with severe immunodeficiencies, upper and lower respiratory infections are most common. However, intestinal and urinary tract infections have been seen alongside various more rare infections such as viral encephalitis. There are a variety of rare DADA2 symptoms that have only been reported in a handful of patients. For example, lymphoproliferation and large granular lymphocytic leukemia have been reported. Other symptoms are becoming more known over time – reports of hypertension associated with DADA2 have increased in recent years.
Adenosine deaminase 2 deficiency
Adenosine deaminase deficiency
Adenine phosphoribosyltransferase deficiency
Adenosine monophosphate deaminase deficiency type 1
Guanidinoacetate methyltransferase deficiency
Galactose-1-phosphate uridylyltransferase deficiency
Aminoacylase 1 deficiency
Methylenetetrahydrofolate reductase deficiency