ArticleGenetics in medicine : official journal of the American College of Medical Genetics2020
The natural history of infantile mitochondrial DNA depletion syndrome due to RRM2B deficiency.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04802707 (A Phase II, Monocenter, Single Arm Study To Assess The Safety and Efficacy Of Combination Deoxycytidine and Deoxythymidine For Mitochondrial Depletion Disorders), which is not on this map. Cited by 8 papers.
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The trial behind it
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A Phase II, Monocenter, Single Arm Study To Assess The Safety and Efficacy Of Combination Deoxycytidine and Deoxythymidine For Mitochondrial Depletion Disorders
Who cites it
8 citing papers in PubMed, 22 citations in OpenAlex.
- RRM2B deficiency causes dATP and dGTP depletion through enhanced degradation and slower synthesis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Mitochondrial Chronic Progressive External Ophthalmoplegia.Brain sciences · 2024Review
- Biomarkers of mitochondrial disorders.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Case Report: A novelFrontiers in pediatrics · 2024Article
- Impact of N221S missense mutation in human ribonucleotide reductase small subunit b on mitochondrial DNA depletion syndrome.Scientific reports · 2023Article
- A novelMolecular genetics and metabolism reports · 2022Article
- Molecular Genetics Overview of Primary Mitochondrial Myopathies.Journal of clinical medicine · 2022Review
- The single nucleotide variant at c.662A>G in human RRM2B is a loss-of-function mutation.Molecular genetics & genomic medicine · 2020Article
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Authors and funding
24 authors at 12 institutions in 3 countries.
Funding
Abstract
purposeMitochondrial DNA (mtDNA) depletion syndrome (MDDS) encompasses a group of genetic disorders of mtDNA maintenance. Mutation of RRM2B is an uncommon cause of infantile-onset encephalomyopathic MDDS. Here we describe the natural history of this disease.
methodsMultinational series of new genetically confirmed cases from six pediatric centers.
resultsNine new cases of infantile-onset RRM2B deficiency, and 22 previously published cases comprised a total cohort of 31 patients. Infants presented at a mean of 1.95 months with truncal hypotonia, generalized weakness, and faltering growth. Seizures evolved in 39% at a mean of 3.1 months. Non-neurological manifestations included respiratory distress/failure (58%), renal tubulopathy (55%), sensorineural hearing loss (36%), gastrointestinal disturbance (32%), eye abnormalities (13%), and anemia (13%). Laboratory features included elevated lactate (blood, cerebrospinal fluid (CSF), urine, magnetic resonance (MR), spectroscopy), ragged-red and cytochrome c oxidase-deficient fibers, lipid myopathy, and multiple oxidative phosphorylation enzyme deficiencies in skeletal muscle. Eight new RRM2B variants were identified. Patients with biallelic truncating variants had the worst survival. Overall survival was 29% at 6 months and 16% at 1 year.
conclusionsInfantile-onset MDDS due to RRM2B deficiency is a severe disorder with characteristic clinical features and extremely poor prognosis. Presently management is supportive as there is no effective treatment. Novel treatments are urgently needed.
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