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

Abstract

Background

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.

Methods

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.

Results

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).

Conclusion

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.

Keywords

Alpers Anaemia Haematopoietic dysfunction Iron metabolism Mitochondria POLG 

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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