The Phenotypic Spectrum of 47 Czech Patients with Single, Large-Scale Mitochondrial DNA Deletions.

Nicole Anteneová,Markéta Tesařová,Hana Kolářová,Petra Lišková,Jiří Zeman,Silvie Kelifová,Alžběta Vondráčková,Hana Hansíková,Iveta Tóthová,Tomáš Honzík,Martin Magner,Josef Zámečník

doi:10.3390/brainsci10110766

Abstract

Background: In this retrospective study, we analysed clinical, biochemical and molecular genetic data of 47 Czech patients with Single, Large-Scale Mitochondrial DNA Deletions (SLSMD). Methods: The diagnosis was based on the long-range PCR (LX-PCR) screening of mtDNA isolated from muscle biopsy in 15 patients, and from the buccal swab, urinary epithelial cells and blood in 32 patients. Results: A total of 57% patients manifested before the age of 16. We did not find any significant difference between paediatric and adult manifestation in either the proportion of patients that would develop extraocular symptoms, or the timespan of its progression. The survival rate in patients with Pearson Syndrome reached 60%. Altogether, five patients manifested with atypical phenotype not fulfilling the latest criteria for SLSMD. No correlation was found between the disease severity and all heteroplasmy levels, lengths of the deletion and respiratory chain activities in muscle. Conclusions: Paediatric manifestation of Progressive External Ophthalmoplegia (PEO) is not associated with a higher risk of multisystemic involvement. Contrary to PEO and Kearns-Sayre Syndrome Spectrum, Pearson Syndrome still contributes to a significant childhood mortality. SLSMD should be considered even in cases with atypical presentation. To successfully identify carriers of SLSMD, a repeated combined analysis of buccal swab and urinary epithelial cells is needed.

Highlights

Single, Large-Scale Mitochondrial DNA Deletions (SLSMD) are common causes of multisystem mitochondrial diseases typically associated with Kearns-Sayre Syndrome (KSS) Spectrum, ProgressiveExternal Ophthalmoplegia (PEO) and Pearson Syndrome [1,2]
Despite the fact that SLSMD are nowadays considered as having the age of onset occurring anytime from infancy to adulthood, more than half of our patients were diagnosed before the age of 16 [2,17,18], making it still a childhood disease with a need of its consideration in any progressive multisystemic disease in a paediatric patient
Transfusion-dependent sideroblastic anaemia is a key finding in Pearson Syndrome [11], we report a patient with failure to thrive as a leading complaint and only mild sideroblastic anaemia with sideroblasts in bone marrow requiring only single transfusion at the age of five

Summary

Introduction

Large-Scale Mitochondrial DNA Deletions (SLSMD) are common causes of multisystem mitochondrial diseases typically associated with Kearns-Sayre Syndrome (KSS) Spectrum, ProgressiveExternal Ophthalmoplegia (PEO) and Pearson Syndrome [1,2]. Large-Scale Mitochondrial DNA Deletions (SLSMD) are common causes of multisystem mitochondrial diseases typically associated with Kearns-Sayre Syndrome (KSS) Spectrum, Progressive. Brain Sci. 2020, 10, 766; doi:10.3390/brainsci10110766 www.mdpi.com/journal/brainsci. Brain Sci. 2020, 10, 766 of transmission from mother to offspring [4]. (Single-Stranded DNA-Binding Protein 1) was recently described, causing SLSMD with clinical symptomatology of Pearson Syndrome, KSS and Leigh syndrome [5]. The exact prevalence is unknown, but it has been estimated at 1.5: 100,000 [8]. In this retrospective study, we analysed clinical, biochemical and molecular genetic data of 47 Czech patients with Single, Large-Scale Mitochondrial DNA Deletions (SLSMD)

Methods

Results

Discussion

Conclusion