RRM2B-MDS is a rare condition; the exact prevalence is unknown. At least 15 cases have been reported in the medical literature.

As the condition name suggests, mutations in the RRM2B gene cause RRM2B-MDS. The RRM2B gene provides instructions for making one piece, called the p53 inducible small subunit (p53R2), of a protein called ribonucleotide reductase (RNR). RNR helps produce DNA building blocks (nucleotides), which are joined to one another in a particular order to form DNA.

RNRs containing p53R2 make nucleotides that are used for the formation of DNA in specialized cell structures called mitochondria. Although most DNA is packaged in chromosomes within the cell's nucleus (nuclear DNA), mitochondria also have a small amount of their own DNA (mitochondrial DNA or mtDNA). Mitochondria are the energy-producing centers in cells, and the DNA in these structures contains genes essential for the process of energy production (called oxidative phosphorylation). The production of nucleotides by p53R2 helps maintain a normal amount of mtDNA in cells.

RRM2B gene mutations reduce the activity or amount of RNR, which likely impairs production of mtDNA nucleotides. A shortage of nucleotides available for the production of mtDNA molecules leads to a reduction in the amount of mtDNA (known as mtDNA depletion), which impairs mitochondrial function.

It is unclear why mtDNA depletion particularly affects the brain and kidneys in people with RRM2B-MDS, but the high energy demands of these tissues may make them especially susceptible to cell death when mtDNA is lost and less energy is produced in cells.