TY - JOUR
T1 - Simplifying the clinical classification of polymerase gamma (POLG) disease based on age of onset; studies using a cohort of 155 cases
AU - Hikmat, Omar
AU - Naess, Karin
AU - Engvall, Martin
AU - Klingenberg, Claus
AU - Rasmussen, Magnhild
AU - Tallaksen, Chantal M. E.
AU - Brodtkorb, Eylert
AU - Ostergaard, Elsebet
AU - de Coo, I. F. M.
AU - Pias-Peleteiro, Leticia
AU - Isohanni, Pirjo
AU - Uusimaa, Johanna
AU - Darin, Niklas
AU - Rahman, Shamima
AU - Bindoff, Laurence A.
N1 - Funding Information:
This work was supported by grants from the Western Norway Regional Health Authority (Helse‐Vest, grant no. 911944). P.I. is supported by grant from the special governmental subsidy for health sciences research of the Helsinki University Hospital. S.R. is supported by research grant funding from Great Ormond Street Hospital Children's Charity, the NIHR Great Ormond Street Hospital Biomedical Research Centre, and the Lily Foundation. I.d.C. was supported by the NeMO foundation (no.17_P19). We would also thank professor Geir Egil Eide, Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway for his help with some of the statistical analysis.
Funding Information:
information Helse Vest Regionalt Helsef?retak, Grant/Award Number: 91144; NeMO foundation, Grant/Award Number: 17_P19; Lily Foundation; NIHR Great Ormond Street Hospital Biomedical Research Centre; Great Ormond Street Hospital Children's CharityThis work was supported by grants from the Western Norway Regional Health Authority (Helse-Vest, grant no. 911944). P.I. is supported by grant from the special governmental subsidy for health sciences research of the Helsinki University Hospital. S.R. is supported by research grant funding from Great Ormond Street Hospital Children's Charity, the NIHR Great Ormond Street Hospital Biomedical Research Centre, and the Lily Foundation. I.d.C. was supported by the NeMO foundation (no.17_P19). We would also thank professor Geir Egil Eide, Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway for his help with some of the statistical analysis.
Publisher Copyright:
© 2020 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM
PY - 2020/7
Y1 - 2020/7
N2 - Background Variants inPOLGare one of the most common causes of inherited mitochondrial disease. Phenotypic classification of POLG disease has evolved haphazardly making it complicated and difficult to implement in everyday clinical practise. The aim of our study was to simplify the classification and facilitate better clinical recognition. Methods A multinational, retrospective study using data from 155 patients withPOLGvariants recruited from seven European countries. Results We describe the spectrum of clinical features associated withPOLGvariants in the largest known cohort of patients. While clinical features clearly form a continuum, stratifying patients simply according to age of onset-onset prior to age 12 years; onset between 12 and 40 years and onset after the age of 40 years, permitted us to identify clear phenotypic and prognostic differences. Prior to 12 years of age, liver involvement (87%), seizures (84%), and feeding difficulties (84%) were the major features. For those with onset between 12 and 40 years, ataxia (90%), peripheral neuropathy (84%), and seizures (71%) predominated, while for those with onset over 40 years, ptosis (95%), progressive external ophthalmoplegia (89%), and ataxia (58%) were the major clinical features. The earlier the onset the worse the prognosis. Patients with epilepsy and those with compound heterozygous variants carried significantly worse prognosis. Conclusion Based on our data, we propose a simplified POLG disease classification, which can be used to guide diagnostic investigations and predict disease course.
AB - Background Variants inPOLGare one of the most common causes of inherited mitochondrial disease. Phenotypic classification of POLG disease has evolved haphazardly making it complicated and difficult to implement in everyday clinical practise. The aim of our study was to simplify the classification and facilitate better clinical recognition. Methods A multinational, retrospective study using data from 155 patients withPOLGvariants recruited from seven European countries. Results We describe the spectrum of clinical features associated withPOLGvariants in the largest known cohort of patients. While clinical features clearly form a continuum, stratifying patients simply according to age of onset-onset prior to age 12 years; onset between 12 and 40 years and onset after the age of 40 years, permitted us to identify clear phenotypic and prognostic differences. Prior to 12 years of age, liver involvement (87%), seizures (84%), and feeding difficulties (84%) were the major features. For those with onset between 12 and 40 years, ataxia (90%), peripheral neuropathy (84%), and seizures (71%) predominated, while for those with onset over 40 years, ptosis (95%), progressive external ophthalmoplegia (89%), and ataxia (58%) were the major clinical features. The earlier the onset the worse the prognosis. Patients with epilepsy and those with compound heterozygous variants carried significantly worse prognosis. Conclusion Based on our data, we propose a simplified POLG disease classification, which can be used to guide diagnostic investigations and predict disease course.
KW - Alpers syndrome
KW - epilepsy
KW - mitochondrial disease
KW - POLG
KW - stroke-like episodes
KW - MUTATIONS
KW - SPECTRUM
KW - PARKINSONISM
U2 - 10.1002/jimd.12211
DO - 10.1002/jimd.12211
M3 - Article
C2 - 32391929
SN - 0141-8955
VL - 43
SP - 726
EP - 736
JO - Journal of Inherited Metabolic Disease
JF - Journal of Inherited Metabolic Disease
IS - 4
ER -