scholarly journals Late-onset presentation of POLG1-associated mitochondrial disease

2019 ◽  
Vol 12 (3) ◽  
pp. e228482 ◽  
Author(s):  
Bruna Meira ◽  
Rafael Roque ◽  
Miguel Pinto ◽  
André Caetano
Keyword(s):  
Mitochondrial Disease ◽  
Age Of Onset ◽  
Late Onset ◽  
Clinical Manifestations ◽  
Progressive External Ophthalmoplegia ◽  
Clinical Feature ◽  
Gait Ataxia ◽  
Chronic Progressive External Ophthalmoplegia ◽  
Genetic Studies ◽  
In Cis

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.

Clinical and molecular spectrum associated with Polymerase-γ related disorders

2022 ◽  
pp. 088307382110670
Author(s):  
Ruchika Jha ◽  
Harshkumar Patel ◽  
Rachana Dubey ◽  
Jyotindra N. Goswami ◽  
Chandana Bhagwat ◽  
...  
Keyword(s):  
Age Of Onset ◽  
Pediatric Population ◽  
Single Gene ◽  
Management Strategies ◽  
Clinical Manifestations ◽  
Progressive External Ophthalmoplegia ◽  
Leigh Disease ◽  
Pathogenic Variants ◽  
Phenotype Analysis

Background POLG pathogenic variants are the commonest single-gene cause of inherited mitochondrial disease. However, the data on clinicogenetic associations in POLG-related disorders are sparse. This study maps the clinicogenetic spectrum of POLG-related disorders in the pediatric population. Methods Individuals were recruited across 6 centers in India. Children diagnosed between January 2015 and August 2020 with pathogenic or likely pathogenic POLG variants and age of onset <15 years were eligible. Phenotypically, patients were categorized into Alpers-Huttenlocher syndrome; myocerebrohepatopathy syndrome; myoclonic epilepsy, myopathy, and sensory ataxia; ataxia-neuropathy spectrum; Leigh disease; and autosomal dominant / recessive progressive external ophthalmoplegia. Results A total of 3729 genetic reports and 4256 hospital records were screened. Twenty-two patients with pathogenic variants were included. Phenotypically, patients were classifiable into Alpers-Huttenlocher syndrome (8/22; 36.4%), progressive external ophthalmoplegia (8/22; 36.4%), Leigh disease (2/22; 9.1%), ataxia-neuropathy spectrum (2/22; 9.1%), and unclassified (2/22; 9.1%). The prominent clinical manifestations included developmental delay (n = 14; 63.7%), neuroregression (n = 14; 63.7%), encephalopathy (n = 11; 50%), epilepsy (n = 11; 50%), ophthalmoplegia (n = 8; 36.4%), and liver dysfunction (n = 8; 36.4%). Forty-four pathogenic variants were identified at 13 loci, and these were clustered at exonuclease (18/44; 40.9%), linker (13/44; 29.5%), polymerase (10/44; 22.7%), and N-terminal domains (3/44; 6.8%). Genotype-phenotype analysis suggested that serious outcomes including neuroregression (odds ratio [OR] 11, 95% CI 2.5, 41), epilepsy (OR 9, 95% CI 2.4, 39), encephalopathy (OR 5.7, 95% CI 1.4, 19), and hepatic dysfunction (OR 4.6, 95% CI 21.3, 15) were associated with at least 1 variant involving linker or polymerase domain. Conclusions We describe the clinical subgroups and their associations with different POLG domains. These can aid in the development of follow-up and management strategies of presymptomatic individuals.

scholarly journals Kearns Sayer Syndrome- A Case Report

2020 ◽  
Vol 6 (6) ◽  
pp. 271-272
Author(s):  
Reshmi Mishra ◽  
Keyword(s):  
Case Report ◽  
Mitochondrial Disease ◽  
Prevalence Rate ◽  
Rare Case ◽  
Age Of Onset ◽  
Progressive External Ophthalmoplegia ◽  
Pigmentary Retinopathy ◽  
Kearns Sayre Syndrome

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.

scholarly journals Kearns-Sayre Syndrome: A Rare Mitochondrial Disorder

2017 ◽  
Vol 19 (1) ◽  
pp. 66-69
Author(s):  
Quazi Tarikul Islam ◽  
Homayra Tahseen Hossain ◽  
Md Abul Kashem Khandaker ◽  
HAM Nazmul Ahasan ◽  
Maksudul Majumder ◽  
...  
Keyword(s):  
Mitochondrial Disease ◽  
Mitochondrial Disorder ◽  
Progressive External Ophthalmoplegia ◽  
Endocrine Disorders ◽  
Chronic Progressive External Ophthalmoplegia ◽  
Diagnostic Investigation ◽  
Kearns Sayre Syndrome ◽  
First Case ◽  
Wide Range ◽  
Clinical Background

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

scholarly journals Late-onset Huntington’s disease with 40–42 CAG expansion

2019 ◽  
Vol 41 (4) ◽  
pp. 869-876 ◽  
Author(s):  
Elisa Capiluppi ◽  
Luca Romano ◽  
Paola Rebora ◽  
Lorenzo Nanetti ◽  
Anna Castaldo ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Rating Scale ◽  
Neurodegenerative Disorder ◽  
Age Of Onset ◽  
Late Onset ◽  
Age At Onset ◽  
Clinical Manifestations ◽  
Cag Repeats ◽  
Cag Expansion

Abstract Introduction Huntington’s disease (HD) is a rare autosomal dominant neurodegenerative disorder caused by a CAG expansion greater than 35 in the IT-15 gene. There is an inverse correlation between the number of pathological CAG and the age of onset. However, CAG repeats between 40 and 42 showed a wider onset variation. We aimed to investigate potential clinical differences between patients with age at onset ≥ 60 years (late onset-HD) and patients with age at onset between 30 and 59 years (common-onset HD) in a cohort of patients with the same CAG expansions (40–42). Methods A retrospective analysis of 66 HD patients with 40–41–42 CAG expansion was performed. Patients were investigated with the Unified Huntington’s Disease Rating Scale (subitems I–II–III and Total Functional Capacity, Functional Assessment and Stage of Disease). Data were analysed using χ2, Fisher’s test, t test and Pearson’s correlation coefficient. GENMOD analysis and Kaplan-Meier analysis were used to study the disease progression. Results The age of onset ranged from 39 to 59 years in the CO subgroup, whereas the LO subgroup showed an age of onset from 60 to 73 years. No family history was reported in 31% of the late-onset in comparison with 20% in common-onset HD (p = 0.04). No difference emerged in symptoms of onset, in clinical manifestations and in progression of disease between the two groups. Conclusion There were no clinical differences between CO and LO subgroups with 40–42 CAG expansion. There is a need of further studies on environmental as well genetic variables modifying the age at onset.

scholarly journals Idiopathic very late-onset cerebellar ataxia: a Brazilian case series

2015 ◽  
Vol 73 (11) ◽  
pp. 903-905 ◽  
Author(s):  
Hélio A. G. Teive ◽  
Mariana Moscovich ◽  
Adriana Moro ◽  
Marina Farah ◽  
Walter O. Arruda ◽  
...  
Keyword(s):  
Cerebellar Ataxia ◽  
Visual Loss ◽  
Age Of Onset ◽  
Late Onset ◽  
Brain Mri ◽  
Cerebellar Atrophy ◽  
Case Series ◽  
Gait Ataxia ◽  
The One ◽  
Brazilian Case

ABSTRACTThe authors present a Brazilian case series of eight patients with idiopathic very-late onset (mean 75.5 years old) cerebellar ataxia, featuring predominantly gait ataxia, associated with cerebellar atrophy.Method: 26 adult patients with a diagnosis of idiopathic late onset cerebellar ataxia were analyzed in a Brazilian ataxia outpatient clinic and followed regularly over 20 years. Among them, 8 elderly patients were diagnosed as probable very late onset cerebellar ataxia. These patients were evaluated with neurological, ophthalmologic and Mini-Mental Status examinations, brain MRI, and EMG.Results: 62.5% of patients were males, mean age was 81.9 years-old, and mean age of onset was 75.5 years. Gait cerebellar ataxia was observed in all patients, as well as, cerebellar atrophy on brain MRI. Mild cognitive impairment and visual loss, due to macular degeneration, were observed in 50% of cases. Chorea was concomitantly found in 3 patients.Conclusion: We believe that this condition is similar the one described by Marie-Foix-Alajouanine presenting with mild dysarthria, associated with gait ataxia, and some patients had cognitive dysfunction and chorea.

scholarly journals Multisystem Disorder in Late-Onset Chronic Progressive External Ophthalmoplegia

2011 ◽  
Vol 38 (1) ◽  
pp. 119-123 ◽  
Author(s):  
Gerald Pfeffer ◽  
Sandra Sirrs ◽  
N. Kevin Wade ◽  
Michelle M. Mezei
Keyword(s):  
Late Onset ◽  
Retrospective Chart Review ◽  
Cardiac Conduction ◽  
Progressive External Ophthalmoplegia ◽  
Chronic Progressive External Ophthalmoplegia ◽  
Mitochondrial Toxicity ◽  
Hepatitis C Infection ◽  
Multisystem Disorder ◽  
Pigmentary Retinopathy ◽  
Disease Spectrum

Abstract:Introduction:Chronic progressive external ophthalmoplegia (CPEO) is a mitochondrial syndrome on a disease spectrum with Kearns-Sayre syndrome (KSS). Clinical presentation is variable and our experience suggested that phenotypic differences exist in CPEO with onset after age 20.Methods:This descriptive study is a retrospective chart review of 40 patients with late-onset CPEO. Clinical features, laboratory and neurophysiology results were reviewed.Results:Multisystem dysfunction was very common in this series. Gastrointestinal dysfunction was more common than expected (60%) as was migraine headache (40%). Clinical characteristics on the KSS disease spectrum were uncommon in this series with only 2.5% having pigmentary retinopathy, 5% with cardiac conduction abnormality, and 22.5% having endocrinopathy (most often thyroid dysfunction rather than diabetes). Neurophysiology abnormalities included length-dependent axonal polyneuropathy in 44% (sometimes subclinical) and myopathic EMG changes in 26%. Exposure to sources of acquired mitochondrial toxicity including cigarette use and hepatitis C infection were more common than expected in this series.Discussion:Phenotype was different in this late-onset series compared with previous reports in CPEO patients. In this series of late-onset patients, multi-organ dysfunction was more common than previously reported in CPEO, and some classical mitochondrial manifestations, such as pigmentary retinopathy were rare. We suggest that acquired mitochondrial toxicity may have a role in the pathogenesis of adult-onset CPEO.

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