YARS2 encodes the mitochondrial
tyrosyl-tRNA synthetase that catalyzes the covalent binding of
tyrosine to its cognate mt-
tRNA. Mutations in YARS2 have been identified in patients with
myopathy,
lactic acidosis, and
sideroblastic anemia type 2 (MLASA2). We report here on two siblings with a novel mutation and a review of literature. The older patient presented at 2 months with marked
anemia and lactic acidemia. He required periodic
blood transfusions until 14 months of age. Cognitive and motor development was normal. His younger sister was diagnosed at birth, presenting with
anemia and
lactic acidosis at 1 month of age requiring periodical transfusions. She is now 14 months old and doing well. For both our patients, there was no clinical evidence of muscle involvement. We found a new homozygous mutation in YARS2, located in the α-
anticodon-binding (αACB) domain, involved in the interaction with the
anticodon of the cognate mt-
tRNA(Tyr).Our study confirms that
MLASA must be considered in patients with congenital
sideroblastic anemia and underlines the importance of early diagnosis and supportive
therapy in order to prevent severe complications. Clinical severity is variable among YARS2-reported patients: our review of the literature suggests a possible phenotype-genotype correlation, although this should be confirmed in a larger population.