Spectrum of movement disorders and neurotransmitter abnormalities in paediatric <i>POLG</i> disease

Papandreou, Apostolos; Rahman, Shamima; Fratter, Carl; Ng, Joanne; Meyer, Esther; Carr, Lucinda; Champion, Michael; Clarke, Antonia; Gissen, Paul; Hemingway, Cheryl; Hussain, Nahin; Jayawant, Sandeep; King, Mary D.; Lynch, Bryan; Mewasingh, Leena; Patel, Jayesh; Prabhakar, P; Neergheen, Viruna; Pope, Simon; Heales, Simon; Poulton, Joanna; Kurian, Manju A.

doi:10.1007/s10545-018-0227-7

Cited by 13 publications

(14 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Epilepsia partialis continua (or EPC) has been well described in children with POLG mutations alongside other movement disorders. 8 Characteristic EEG changes of rhythmic high-amplitude delta with superimposed polyspikes as reported previously in POLG-related disorders 9 were seen in three children with POLG mutation only. Although both background abnormalities and epileptiform discharges in the unaffected hemisphere have been reported in 25%-62% of cases of RE 6 months after onset of seizures, 7 this was seen only on EEG at EPC onset in 2 of 30 of our children with RE, suggesting this may be a later feature of RE.…”

Section: Discussionsupporting

confidence: 63%

See 1 more Smart Citation

Diagnostic algorithm for children presenting with epilepsia partialis continua

et al. 2020

View full text Add to dashboard Cite

Objective: To characterize a cohort of children with epilepsia partialis continua (EPC) and develop a diagnostic algorithm incorporating key differential diagnoses. Methods: Children presenting with EPC to a tertiary pediatric neurology center between 2002 and 2019 were characterized. Results: Fifty-four children fulfilled EPC criteria. Median age at onset was 7 years (range 0.6-15), with median follow-up of 4.3 years (range 0.2-16). The diagnosis was Rasmussen encephalitis (RE) in 30 of 54 (56%), a mitochondrial disorder in 12

show abstract

Section: Discussionsupporting

confidence: 63%

“…Epilepsia partialis continua (or EPC) has been well described in children with POLG mutations alongside other movement disorders 8 . Characteristic EEG changes of rhythmic high‐amplitude delta with superimposed polyspikes as reported previously in POLG‐related disorders 9 were seen in three children with POLG mutation only.…”

Section: Discussionsupporting

confidence: 54%

Diagnostic algorithm for children presenting with epilepsia partialis continua

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Only nonspecific changes were found. Secondary neurotransmitter abnormalities are frequently found in children with MDs (García-Cazorla et al, 2007; Tonduti et al, 2015; Burlina et al, 2017), and abnormal patterns suggestive of specific conditions other than primary defects have been recently described (Peall et al, 2017; Papandreou et al, 2018). Nevertheless, most of the commonly encountered secondary neurotransmitters abnormalities still lack a specific diagnostic value.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic Yield of a Targeted Next-Generation Sequencing Gene Panel for Pediatric-Onset Movement Disorders: A 3-Year Cohort Study

et al. 2019

View full text Add to dashboard Cite

In recent years, genetic techniques of diagnosis have shown rapid development, resulting in a modified clinical approach to many diseases, including neurological disorders. Movement disorders, in particular those arising in childhood, pose a diagnostic challenge. First, from a purely phenomenological point of view, the correct clinical classification of signs and symptoms may be difficult and require expert evaluation. This is because the clinical picture is often a mixture of hyperkinetic and hypokinetic disorders, and within hyperkinetic movement disorders, combined phenotypes are not unusual. Second, although several genes that cause movement disorders in children are now well-known, many of them have only been described in adult populations or discovered in patients after many years of disease. Furthermore, diseases that alter their mechanisms from childhood to adulthood are still little known, and many phenotypes in children are the result of a disruption of normal neurodevelopment. High-throughput gene screening addresses these difficulties and has modified the approach to genetic diagnosis. In the exome-sequencing era, customized genetic panels now offer the ability to perform fast and low-cost screening of the genes commonly involved in the pathogenesis of the disease. Here, we describe a 3-year study using a customized gene panel for pediatric-onset movement disorders in a selected cohort of children and adolescents. We report a satisfying diagnostic yield, further confirming the usefulness of gene panel analysis.

show abstract

“…Chronic immune response activation is one possible cause of increased oxidative stress and interestingly there have been some reports of CFD associated with elevated levels of the immune response activation marker, neopterin. 76,106,107 In our laboratory, we have noticed that in some CSF samples 5-MTHF degrades rapidly on the HPLC autosampler (unpublished findings) even though 5-MTHF is typically thought to be relatively stable in biological samples. 34 This may suggest that in some samples, antioxidant defenses are compromised and/or oxidizing species are present in the CSF.…”

Section: Oxidative Stress and Toxic Insult Resulting In Cfdmentioning

confidence: 91%

Cerebral folate deficiency: Analytical tests and differential diagnosis

Pope

Artuch

Heales

et al. 2019

J of Inher Metab Disea

View full text Add to dashboard Cite

Cerebral folate deficiency is typically defined as a deficiency of the major folate species 5‐methyltetrahydrofolate in the cerebrospinal fluid (CSF) in the presence of normal peripheral total folate levels. However, it should be noted that cerebral folate deficiency is also often used to describe conditions where CSF 5‐MTHF is low, in the presence of low or undefined peripheral folate levels. Known defects of folate transport are deficiency of the proton coupled folate transporter, associated with systemic as well as cerebral folate deficiency, and deficiency of the folate receptor alpha, leading to an isolated cerebral folate deficiency associated with intractable seizures, developmental delay and/or regression, progressive ataxia and choreoathetoid movement disorders. Inborn errors of folate metabolism include deficiencies of the enzymes methylenetetrahydrofolate reductase, dihydrofolate reductase and 5,10‐methenyltetrahydrofolate synthetase. Cerebral folate deficiency is potentially a treatable condition and so prompt recognition of these inborn errors and initiation of appropriate therapy is of paramount importance. Secondary cerebral folate deficiency may be observed in other inherited metabolic diseases, including disorders of the mitochondrial oxidative phosphorylation system, serine deficiency, and pyridoxine dependent epilepsy. Other secondary causes of cerebral folate deficiency include the effects of drugs, immune response activation, toxic insults and oxidative stress. This review describes the absorption, transport and metabolism of folate within the body; analytical methods to measure folate species in blood, plasma and CSF; inherited and acquired causes of cerebral folate deficiency; and possible treatment options in those patients found to have cerebral folate deficiency.

show abstract

Spectrum of movement disorders and neurotransmitter abnormalities in paediatric POLG disease

Abstract: Children with POLG mutations can manifest with a wide spectrum of abnormal movements, which are often prominent features of the clinical syndrome. Underlying pathophysiology is probably multifactorial, and aberrant monoamine metabolism is likely to play a role.

Cited by 13 publications

References 25 publications

Diagnostic algorithm for children presenting with epilepsia partialis continua

Diagnostic algorithm for children presenting with epilepsia partialis continua

Diagnostic Yield of a Targeted Next-Generation Sequencing Gene Panel for Pediatric-Onset Movement Disorders: A 3-Year Cohort Study

Cerebral folate deficiency: Analytical tests and differential diagnosis

Contact Info

Product

Resources

About