Journal of Inherited Metabolic Disease

, Volume 40, Issue 6, pp 861–866 | Cite as

The presence of anaemia negatively influences survival in patients with POLG disease

  • Omar Hikmat
  • Tzoulis Charalampos
  • Claus Klingenberg
  • Magnhild Rasmussen
  • Chantal M. E. Tallaksen
  • Eylert Brodtkorb
  • Torunn Fiskerstrand
  • Robert McFarland
  • Shamima Rahman
  • Laurence A. Bindoff
Original Article



Mitochondria play an important role in iron metabolism and haematopoietic cell homeostasis. Recent studies in mice showed that a mutation in the catalytic subunit of polymerase gamma (POLG) was associated with haematopoietic dysfunction including anaemia. The aim of this study was to analyse the frequency of anaemia in a large cohort of patients with POLG related disease.


We conducted a multi-national, retrospective study of 61 patients with confirmed, pathogenic biallelic POLG mutations from six centres, four in Norway and two in the United Kingdom. Clinical, laboratory and genetic data were collected using a structured questionnaire. Anaemia was defined as an abnormally low haemoglobin value adjusted for age and sex. Univariate survival analysis was performed using log-rank test to compare differences in survival time between categories.


Anaemia occurred in 67% (41/61) of patients and in 23% (14/61) it was already present at clinical presentation. The frequency of anaemia in patients with early onset disease including Alpers syndrome and myocerebrohepatopathy spectrum (MCHS) was high (72%) and 35% (8/23) of these had anaemia at presentation. Survival analysis showed that the presence of anaemia was associated with a significantly worse survival (P = 0.004).


Our study reveals that anaemia can be a feature of POLG-related disease. Further, we show that its presence is associated with significantly worse prognosis either because anaemia itself is impacting survival or because it reflects the presence of more serious disease. In either case, our data suggests anaemia is a marker for negative prognosis.


Alpers Anaemia Haematopoietic dysfunction Iron metabolism Mitochondria POLG 



This work was supported by grants from the Western Norway Regional Health Authority (Helse Vest, grants no.911944). We would also thank statistician adjunct professor Geir Egil Eide, department of Global Public Health and Primary Care, Bergen University, Bergen, Norway for help with statistics analysis.

Compliance with ethical standards

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000(5). The ethical approved for the study was obtained from the Regional committee for Medical and Health Research Ethics, western Norway (REK 2014/17833-4). The study was registered as an audit at Great Ormond Street Hospital, London, UK. Anonymised data regarding Newcastle patients was provided courtesy of the MRC Mitochondrial Disease Patient Cohort (Ethics ref:13/NE/0326).

Conflicts of interest

O. Hikmat, T. Charalampos, C. Klingenberg, M. Rasmussen, C. M. E. Tallaksen, E. Brodtkorb, T. Fiskerstrand, R. McFarland, S. Rahman, and L. A. Bindoff declare that they have no conflict of interest.

Supplementary material

10545_2017_84_MOESM1_ESM.xlsx (13 kb)
ESM 1 (XLSX 13.1 kb)


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Copyright information

© SSIEM 2017

Authors and Affiliations

  • Omar Hikmat
    • 1
    • 2
  • Tzoulis Charalampos
    • 2
    • 3
  • Claus Klingenberg
    • 4
    • 5
  • Magnhild Rasmussen
    • 6
    • 7
  • Chantal M. E. Tallaksen
    • 8
    • 9
  • Eylert Brodtkorb
    • 10
    • 11
  • Torunn Fiskerstrand
    • 12
    • 13
  • Robert McFarland
    • 14
  • Shamima Rahman
    • 15
    • 16
  • Laurence A. Bindoff
    • 2
    • 3
  1. 1.Department of PediatricsHaukeland University HospitalBergenNorway
  2. 2.Department of Clinical Medicine (K1)University of BergenBergenNorway
  3. 3.Department of NeurologyHaukeland University HospitalBergenNorway
  4. 4.Department of Paediatric and Adolescent MedicineUniversity Hospital of North NorwayTromsøNorway
  5. 5.Paediatric Research Group, Department of Clinical MedicineUiT- The Arctic University of NorwayTromsøNorway
  6. 6.Women and Children’s Division, Department of Clinical Neurosciences for ChildrenOslo University HospitalOsloNorway
  7. 7.Unit for Congenital and Hereditary Neuromuscular Disorders, Department of NeurologyOslo University HospitalOsloNorway
  8. 8.Department of NeurologyOslo University HospitalOsloNorway
  9. 9.Institute of Clinical Medicine, Faculty of MedicineUniversity of OsloOsloNorway
  10. 10.Department of NeuroscienceNorwegian University of Science and TechnologyTrondheimNorway
  11. 11.Department of Neurology and Clinical NeurophysiologySt. Olav’s University HospitalTrondheimNorway
  12. 12.Center for Medical Genetics and Molecular MedicineHaukeland University HospitalBergenNorway
  13. 13.Department of Clinical Science (K2)University of BergenBergenNorway
  14. 14.Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, The Medical School Framlington PlaceNewcastle UniversityNewcastle upon TyneUK
  15. 15.Mitochondrial Research GroupUCL Great Ormond Street Institute of Child HealthLondonUK
  16. 16.Metabolic UnitGreat Ormond Street Hospital NHS Foundation trustLondonUK

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