Similar to folate deficiency and MTRR mutations in humans [30,[32], [33], [34]], metabolic derangement caused by Mtrrgt/gt homozygosity in mice is associated with macrocytic anaemia [36] and a wide spectrum of developmental phenotypes (e.g., neural tube defects, cardiac defects, fetal growth restriction) that display incomplete penetrance [35]. Here, MTRR is linked to macrocytic anemia.