Novel RRM2B mutation in association with severe mitochondrial DNA depletion: report of 2 cases and review of the literature

Nesia Kropach ¹ Vered Zemer-Shkalim ⁴ Naama Orenstein ³ Rachel Straussberg ²

¹pediatric department, Schneider Children’s Medical Center of Israel
²Child Neurology unit, Schneider Children’s Medical Center of Israel
³Genetic clinic, Schneider Children’s Medical Center of Israel
⁴The Rina Zaizov Hematology-Oncology Deviosion, Schneider Children’s Medical Center of Israel

Mitochondrial DNA depletion syndromes are characterized by a reduction in the copy number of mitochondrial DNA. Onset is in infancy or childhood. Recently, mutations in the RRM2B gene which encodes the p53- controlled ribonucleotide reductase subunit have been found to be related to MDS. We describe 2 brothers who presented with poor feeding, failure to thrive, severe hypotonia, and lactic acidosis, leading to death due to respiratory failure at ages 3 and 2 months. The older brother also had seizures, and the younger had severe bilateral neurosensory deafness. Genetic sequencing of the RRM2B gene revealed the same novel mutation in both siblings.