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@ARTICLE{Zibold:165165,
      author       = {Zibold, Julia and von Livonius, Bettina and Kolarova, Hana
                      and Rudolph, Günter and Priglinger, Claudia S and
                      Klopstock, Thomas and Catarino, Claudia B},
      title        = {{V}itamin {B}12 in {L}eber hereditary optic neuropathy
                      mutation carriers: a prospective cohort study.},
      journal      = {Orphanet journal of rare diseases},
      volume       = {17},
      number       = {1},
      issn         = {1750-1172},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {DZNE-2022-01467},
      pages        = {310},
      year         = {2022},
      abstract     = {Leber hereditary optic neuropathy (LHON) is the most common
                      mitochondrial disorder, frequently resulting in acute or
                      subacute severe bilateral central vision loss. Vitamin B12
                      deficiency is also a known cause of optic neuropathy through
                      mitochondrial dysfunction. Here we evaluated the prevalence
                      and clinical significance of vitamin B12 deficiency in a
                      large cohort of LHON patients and asymptomatic mutation
                      carriers from a tertiary referral center.From the Munich
                      LHON prospective cohort study, participants included all
                      LHON patients and asymptomatic LHON mutation carriers, who
                      were recruited between February 2014 and March 2020 and
                      consented to participate. Neurological, general, and
                      ophthalmological examinations were regularly performed, as
                      were laboratory tests. Vitamin B12 deficiency was diagnosed
                      if serum vitamin B12 was below 201 pg/mL, or if 201-339
                      pg/mL plus low serum holotranscobalamin or elevated serum
                      methylmalonic acid or elevated total plasma homocysteine.We
                      analyzed 244 subjects, including 147 symptomatic LHON
                      patients $(74\%$ males) and 97 asymptomatic mutation
                      carriers $(31\%$ males). Median age at study baseline was 34
                      years (range 5-82 years). The prevalence of vitamin B12
                      deficiency was higher for LHON mutation carriers than for
                      the general population in all age categories. This was
                      statistically significant for the LHON mutation carriers
                      under 65 years $(21\%$ vs. $5-7\%,$ p = 0.002). While
                      vitamin B12 deficiency prevalence was not statistically
                      different between LHON patients and asymptomatic mutation
                      carriers, its clinical correlates, e.g., macrocytosis and
                      polyneuropathy, were more frequent in the subgroup of LHON
                      patients. Excessive alcohol consumption was a significant
                      predictor of vitamin B12 deficiency (p < 0.05).The high
                      prevalence of vitamin B12 deficiency in LHON mutation
                      carriers, both asymptomatic mutation carriers and LHON
                      patients, highlights the need for regular vitamin B12
                      screening in this population, in order to ensure early
                      treatment, aiming for better outcomes. Our study is not
                      conclusive regarding vitamin B12 deficiency as determinant
                      for disease conversion in LHON, and further research is
                      warranted to disentangle the role of vitamin B12 in the
                      pathophysiology and prognosis of LHON.},
      keywords     = {Adolescent / Adult / Aged / Aged, 80 and over / Child /
                      Child, Preschool / DNA, Mitochondrial: genetics / Female /
                      Humans / Male / Middle Aged / Mutation: genetics / Optic
                      Atrophy, Hereditary, Leber: epidemiology / Optic Atrophy,
                      Hereditary, Leber: genetics / Prospective Studies / Vitamin
                      B 12 / Vitamin B 12 Deficiency: epidemiology / Vitamin B 12
                      Deficiency: genetics / Young Adult / Cobalamin (Other) /
                      Hereditary optic atrophy (Other) / LHON (Other) / Leber
                      optic atrophy (Other) / Mitochondrial disease (Other) /
                      Vitamin B12 (Other) / DNA, Mitochondrial (NLM Chemicals) /
                      Vitamin B 12 (NLM Chemicals)},
      cin          = {AG Höglinger 2},
      ddc          = {610},
      cid          = {I:(DE-2719)1111015},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:35945620},
      pmc          = {pmc:PMC9361590},
      doi          = {10.1186/s13023-022-02453-z},
      url          = {https://pub.dzne.de/record/165165},
}