Simplifying the clinical classification of polymerase gamma (POLG) disease based on age of onset; studies using a cohort of 155 cases

• DOI: 10.1002/jimd.12211
• Publication Date: 2020-01-06T10:36:22Z
• Authors: Omar Hikmat; Karin Naess; Martin Engvall; Claus Klingenberg; Magnhild Rasmussen; Chantal ME Tallaksen; Eylert Brodtkorb; Elsebet Ostergaard; I. F. M de Coo; Leticia Pias‐Pele...; Pirjo Isohanni; Johanna Uusimaa; Niklas Darin; Shamima Rahman; Laurence A. Bindoff
• Keywords: Mitochondrial disease; Clinical phenotype

Variants in POLG are one of the most common causes inherited mitochondrial disease. Phenotypic classification disease has evolved haphazardly making it complicated and difficult to implement everyday clinical practise. The aim our study was simplify facilitate better recognition.A multinational, retrospective using data from 155 patients with variants recruited seven European countries.We describe spectrum features associated largest known cohort patients. While clearly form a continuum, stratifying simply according age onset-onset prior 12 years; onset between 40 years after years, permitted us identify clear phenotypic prognostic differences. Prior age, liver involvement (87%), seizures (84%), feeding difficulties (84%) were major features. For those ataxia (90%), peripheral neuropathy (71%) predominated, while for over ptosis (95%), progressive external ophthalmoplegia (89%), (58%) earlier worse prognosis. Patients epilepsy compound heterozygous carried significantly prognosis.Based on data, we propose simplified classification, which can be used guide diagnostic investigations predict course.