Progressive external ophthalmoplegia. Evidence for a generalized mitochondrial disease with a defect in pyruvate metabolism

1978 ◽  
Vol 22 (6) ◽  
pp. 424
Author(s):  
Thomas Weingeist
2019 ◽  
Vol 12 (3) ◽  
pp. e228482 ◽  
Author(s):  
Bruna Meira ◽  
Rafael Roque ◽  
Miguel Pinto ◽  
André Caetano

Mutations in the nuclear POLG1 gene compromise the integrity of mitochondrial DNA and show great allelic and clinical heterogeneity. Among adult POLG1-associated mitochondrial disease, the main clinical feature is chronic progressive external ophthalmoplegia. Other related clinical manifestations are sensory or cerebellar ataxia, peripheral neuropathy, myopathy or extrapyramidal symptoms. We report the case of a 72-year-old man who presented with a late onset sensory neuronopathy, chronic progressive external ophthalmoplegia, gait ataxia and parkinsonism. Genetic studies showed a compound heterozygosity of known pathogenic mutations in the POLG1 gene (variant T252I/P587 L in cis configuration in allele 1 and variant R807C in allele 2). Late life presentation highlights that mitochondrial disorders should be considered regardless of age of onset of symptoms.


2020 ◽  
Vol 6 (6) ◽  
pp. 271-272
Author(s):  
Reshmi Mishra ◽  

Kearns–Sayre syndrome (KSS) is a rare mitochondrial disease was first described in 1958. The characteristic triad is age of onset less than 20 years, progressive external ophthalmoplegia, pigmentary retinopathy, The prevalence rate of KSS is nearly 1–3 per 100 000 individuals. Here, we report a rare case of a 11-year-old male with KSS.


2017 ◽  
Vol 19 (1) ◽  
pp. 66-69
Author(s):  
Quazi Tarikul Islam ◽  
Homayra Tahseen Hossain ◽  
Md Abul Kashem Khandaker ◽  
HAM Nazmul Ahasan ◽  
Maksudul Majumder ◽  
...  

Mitochondrial disease, once thought to be a rare clinical entity, is now recognized as an important cause of a wide range of neurologic, muscle, cardiac and endocrine disorders. Kearns Sayre syndrome is a rare mitochondrial disease, involving deletion of mitochondrial DNA. This syndrome ischaracterized by progressive external ophthalmoplegia (PEO), retinitis pigmentosa and an onset before the age of 20 years. First case was reported in 1958. We are reporting a case with chronic progressive external ophthalmoplegia, bilateral partial ptosis with onset at 10 years of age. He also had features of myopathy and neuropathy without any fatigable weakness. Our diagnosis is mostly based on clinical background and by exclusion of other common disorders, as definitive diagnostic investigation genetic testing due to unavailability so was not done.J MEDICINE Jan 2018; 19 (1) : 66-69


2017 ◽  
Vol 3 (3) ◽  
pp. e149 ◽  
Author(s):  
Enrico Bugiardini ◽  
Olivia V. Poole ◽  
Andreea Manole ◽  
Alan M. Pittman ◽  
Alejandro Horga ◽  
...  

Objective:Pathologic ribonuclease H1 (RNase H1) causes aberrant mitochondrial DNA (mtDNA) segregation and is associated with multiple mtDNA deletions. We aimed to determine the prevalence of RNase H1 gene (RNASEH1) mutations among patients with mitochondrial disease and establish clinically meaningful genotype-phenotype correlations.Methods:RNASEH1 was analyzed in patients with (1) multiple deletions/depletion of muscle mtDNA and (2) mendelian progressive external ophthalmoplegia (PEO) with neuropathologic evidence of mitochondrial dysfunction, but no detectable multiple deletions/depletion of muscle mtDNA. Clinicopathologic and molecular evaluation of the newly identified and previously reported patients harboring RNASEH1 mutations was subsequently undertaken.Results:Pathogenic c.424G>A p.Val142Ile RNASEH1 mutations were detected in 3 pedigrees among the 74 probands screened. Given that all 3 families had Indian ancestry, RNASEH1 genetic analysis was undertaken in 50 additional Indian probands with variable clinical presentations associated with multiple mtDNA deletions, but no further RNASEH1 mutations were confirmed. RNASEH1-related mitochondrial disease was characterized by PEO (100%), cerebellar ataxia (57%), and dysphagia (50%). The ataxia neuropathy spectrum phenotype was observed in 1 patient. Although the c.424G>A p.Val142Ile mutation underpins all reported RNASEH1-related mitochondrial disease, haplotype analysis suggested an independent origin, rather than a founder event, for the variant in our families.Conclusions:In our cohort, RNASEH1 mutations represent the fourth most common cause of adult mendelian PEO associated with multiple mtDNA deletions, following mutations in POLG, RRM2B, and TWNK. RNASEH1 genetic analysis should also be considered in all patients with POLG-negative ataxia neuropathy spectrum. The pathophysiologic mechanisms by which the c.424G>A p.Val142Ile mutation impairs human RNase H1 warrant further investigation.


2018 ◽  
Vol 25 (6) ◽  
pp. 879-882 ◽  
Author(s):  
Kevin R Patel ◽  
Amel Karaa ◽  
Farrah J Mateen

Evidence from genetic and pathologic studies suggests that mitochondrial dysfunction occurs in multiple sclerosis (MS). Furthermore, cases of MS have been reported in patients with mitochondrial disease. The phenotypic range of mitochondrial illness associating with MS is not yet well defined. In this report, we highlight two cases of patients with confirmed genetic mutations responsible for progressive external ophthalmoplegia who independently meet McDonald criteria for MS. Better characterization of the range of mitochondrial disease associated with MS may improve our understanding of MS disease pathophysiology.


Author(s):  
John H. J. Wokke ◽  
Pieter A. van Doorn ◽  
Jessica E. Hoogendijk ◽  
Marianne de Visser

2021 ◽  
pp. jmedgenet-2021-108006
Author(s):  
Kristoffer Björkman ◽  
John Vissing ◽  
Elsebet Østergaard ◽  
Laurence A Bindoff ◽  
Irenaeus F M de Coo ◽  
...  

BackgroundLarge-scale mitochondrial DNA deletions (LMD) are a common genetic cause of mitochondrial disease and give rise to a wide range of clinical features. Lack of longitudinal data means the natural history remains unclear. This study was undertaken to describe the clinical spectrum in a large cohort of patients with paediatric disease onset.MethodsA retrospective multicentre study was performed in patients with clinical onset <16 years of age, diagnosed and followed in seven European mitochondrial disease centres.ResultsA total of 80 patients were included. The average age at disease onset and at last examination was 10 and 31 years, respectively. The median time from disease onset to death was 11.5 years. Pearson syndrome was present in 21%, Kearns-Sayre syndrome spectrum disorder in 50% and progressive external ophthalmoplegia in 29% of patients. Haematological abnormalities were the hallmark of the disease in preschool children, while the most common presentations in older patients were ptosis and external ophthalmoplegia. Skeletal muscle involvement was found in 65% and exercise intolerance in 25% of the patients. Central nervous system involvement was frequent, with variable presence of ataxia (40%), cognitive involvement (36%) and stroke-like episodes (9%). Other common features were pigmentary retinopathy (46%), short stature (42%), hearing impairment (39%), cardiac disease (39%), diabetes mellitus (25%) and renal disease (19%).ConclusionOur study provides new insights into the phenotypic spectrum of childhood-onset, LMD-associated syndromes. We found a wider spectrum of more prevalent multisystem involvement compared with previous studies, most likely related to a longer time of follow-up.


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