DADA2 is caused by mutations in DNA encoding the gene ADA2, formerly known as CECR1. The ADA2 gene is located on chromosome<unk> 2q11.1. Many different kinds of mutations have been reported, including missense, nonsense, splice-site, frameshift, deletions, and duplications. As of<unk> 021, there are 117 known mutations, although classification into disease-causing and benign is ongoing. This disease is inherited in an autosomal recessive fashion meaning that both versions of this gene, one inherited from each parent, must be defective in a patient. While those with only one known mutant allele have been found to have disease manifestations, it is thought that those individuals have a mutation not found upon initial genomic sequencing. While there is some relationship between the genetic mutations a patient displays and their experience with the disease, the relationship is not one to one. Patients with DADA2 that share the same mutation are more likely to experience similar disease, but even family members with the same mutations have had entirely different disease courses. While the reasons for this difference are not well defined in DADA2 this is common in other so-called monogenic diseases, where environment and modifier genetics have been shown to play a role. However, multiple groups have found some correlation between mutation and phenotype. There is some indication that mutations present in the dimerization domain of ADA2 predispose towards vasculitis-associated disease, whereas mutations in the catalytic domain lead to the Diamond Blackfan anemia-like phenotype. In another study, specific mutations segregated perfectly into groups based on the type of the disease the patient displayed. In this analysis, the common G47R mutation always found in individuals with vasculitic disease, and the G358R mutation always seen in those with severe hematologic disease. However, some mutations did not separate as well. For example, the R169Q mutation was found in both vasculitic- and hematologic-forward disease subtypes. An analysis of the enzymatic activity of mutated ADA2 enzyme in vitro found that mutations yielding greater enzyme activity favored vasculitis, whereas mutations with less residual activity favored hematologic manifestations.
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