Article
Medical Laboratory Technology
Ingrid Florez, Irune Pirrone, Liliana Casique, Carmen Luisa Dominguez, Antonieta Mahfoud, Tania Rodriguez, Daniel Rodriguez, Marisel De Lucca, Jose Luis Ramirez
Summary: Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a progressive neurodegenerative mitochondrial disease caused by nucleotide changes in the mtDNA, with the m.3243A>G mutation being the most common. This study analyzed three Venezuelan patients with MELAS syndrome and found common symptoms of lactic acidosis, cerebral atrophy, and muscular system deficit. The mutation m.3243A>G was confirmed in different body samples with varying degrees of heteroplasmy, indicating independent origins for the mutation among the patients' mitochondrial haplogroups.
CLINICAL BIOCHEMISTRY
(2022)
Article
Geriatrics & Gerontology
Nai-Yi Liao, Kwong-Kum Liao, Yi-Chu Liao, Yi-Chung Lee
Summary: MELAS and CADASIL are two monogenic cerebral small vessel diseases, but the m.3243A>G mutation associated with MELAS is rarely found in patients with CADASIL-like manifestations. Therefore, screening for this mutation in CADASIL patients may not be very useful.
NEUROBIOLOGY OF AGING
(2021)
Article
Endocrinology & Metabolism
Hok-Fung Tong, Han-Chih Hencher Lee, Tsz-Yan Tammy Tong, Siu-Fung Lam, Bun Sheng, Kin-Wah Chan, June Kam-Yin Li, Ho-Kee Vicki Tam, Chor-Kwan Ching
Summary: This study reviewed the diagnosis and management of m.3243A>G-related diabetes and evaluated the risk of metformin use triggering neurological manifestations. The results showed that m.3243A>G-related diabetes is often underdiagnosed, and metformin may trigger neurological manifestations in this condition.
JOURNAL OF DIABETES AND ITS COMPLICATIONS
(2022)
Article
Cell Biology
Xinpei Gao, Zhixin Jiang, Xinfeng Yan, Jiping Liu, Fengwen Li, Peng Liu, Jialu Li, Yuehua Wei, Yi Eve Sun, Yinan Zhang, Congrong Wang
Summary: The study isolated and expanded urine-derived stem cells from patients with the m.3243A>G mutation, finding that cells with high mutation levels exhibited abnormal mitochondrial morphology and function, as well as affected signaling pathways and osteogenic potentials. Knocking down ATF5 improved mitochondrial function and restored osteogenic potentials, suggesting ATF5-dependent UPRmt could be a potential therapeutic target for mitochondrial dysfunction and osteoporosis associated with the m.3243A>G mutation.
CELL DEATH & DISEASE
(2021)
Article
Clinical Neurology
Hiroaki Miyahara, Chisato Tamai, Masanori Inoue, Kazuhito Sekiguchi, Daisuke Tahara, Nao Tahara, Kazuhiro Takeda, Shusei Arafuka, Hideyuki Moriyoshi, Ryuichi Koizumi, Akio Akagi, Yuichi Riku, Jun Sone, Mari Yoshida, Kenji Ihara, Yasushi Iwasaki
Summary: The study found that the m. 3243A>G mutation is closely related to mitochondrial diseases, which can cause mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes. The mutation leads to increased mitochondrial DNA heteroplasmy and decreased activity of oxidative phosphorylation complexes. High levels of mtDNA heteroplasmy and various cortical lesions were observed in the brain tissue. Swelling of smooth muscle cells and increased mitochondrial antibody immunoreactivity in vessels on the leptomeninges, as well as increased cytoplasmic size of epithelial cells in the choroid plexus, could serve as neuropathological hallmarks for the diagnosis of mitochondrial diseases.
Article
Neurosciences
Helin Zheng, Xuemei Zhang, Lu Tian, Bo Liu, Xiaoya He, Longlun Wang, Shuang Ding, Yi Guo, Jinhua Cai
Summary: This study evaluated the neuroimaging findings of MELAS patients and analyzed the possible underlying causes of stroke-like episodes. The results showed that the lesions were mainly located in the posterior brain, with varied signal characteristics, morphology, and temporal evolution. Additionally, MELAS was also associated with basal ganglia calcifications, cerebral and cerebellar atrophy, and elevated lactate levels.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Endocrinology & Metabolism
Karien Esterhuizen, J. Zander Lindeque, Shayne Mason, Francois H. van der Westhuizen, Richard J. Rodenburg, Paul de Laat, Jan A. M. Smeitink, Mirian C. H. Janssen, Roan Louw
Summary: The m.3243A > G mitochondrial DNA mutation is associated with different phenotypes such as MELAS, MIDD, and myopathy, affecting metabolic pathways differently. Analyzing urine metabolomes of patients revealed specific metabolic perturbations and similarities between the different phenotypes, providing insights for potential treatment options.
Review
Biochemistry & Molecular Biology
Sanna Ryytty, Riikka H. Hamalainen
Summary: The m.3243A>G mutation in the MT-TL1 gene is a common point mutation in human mtDNA, with varying symptoms and severity. The reasons for the heterogeneity and limited treatment options are unknown. Cell models, such as patient-derived and cybrid models, have provided insights into the cell-type-specific effects and tolerance of this mutation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Nutrition & Dietetics
Heidi E. E. Zweers, Mirian C. H. Janssen, Geert J. A. Wanten
Summary: The aim of this study was to identify the optimal method for estimating total energy expenditure (TEE) in patients with mitochondrial disease (MD). It was found that TEE in MD patients is lower than recommended for healthy adults due to lower physical activity. Predictive equations (PEs) for resting energy expenditure (REE) provide a reliable alternative to indirect calorimetry (IC) in MD patients, with an accuracy of 71% to 76%. Accelerometry is recommended for measuring PAL in this population as patients' estimations of PAL are highly variable and unreliable.
JOURNAL OF PARENTERAL AND ENTERAL NUTRITION
(2021)
Article
Biochemistry & Molecular Biology
Melissa Franco, Sarah J. Pickett, Zoe Fleischmann, Mark Khrapko, Auden Cote-L'Heureux, Dylan Aidlen, David Stein, Natasha Markuzon, Konstantin Popadin, Maxim Braverman, Dori C. Woods, Jonathan L. Tilly, Doug M. Turnbull, Konstantin Khrapko
Summary: The A-to-G point mutation at position 3243 in the human mitochondrial genome (m.3243A > G) is the most common pathogenic mtDNA variant responsible for disease in humans. It is widely accepted that m.3243A > G levels decrease with age in blood, and a 2% annual decline correction is often applied. However, recent data suggest that the dynamics of m.3243A > G are more complex and depend on the mutation level in blood in a biphasic way. This biphasic approach can greatly improve the accuracy of modeling changes in mtDNA mutation frequencies.
HUMAN MOLECULAR GENETICS
(2022)
Article
Medicine, General & Internal
Xueli Chang, Zhaoxu Yin, Wei Zhang, Jiaying Shi, Chuanqiang Pu, Qiang Shi, Juan Wang, Jing Zhang, Li Yan, Wenqu Yang, Junhong Guo
Summary: The pathogenesis of MELAS syndrome, which involves mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes, remains unclear. This study performed proteomic analysis on skeletal muscle specimens from MELAS patients and identified differential proteins related to oxidative stress, as well as pathways involving phagosome, ribosome, and peroxisome proliferator-activated receptors (PPAR). These findings suggest that the imbalance between oxidative stress and antioxidant defense, as well as abnormal metabolism of mitochondrial ribosome proteins, may play important roles in the development of MELAS syndrome.
Article
Endocrinology & Metabolism
Simone Rask Nielsen, Stinus Gadegaard Hansen, Claus Bistrup, Klaus Brusgaard, Anja Lisbeth Frederiksen
Summary: This case presents a complex clinical phenotype with the rare coincidence of X-linked hypophosphatemic rickets (XLH) and m.3243A>G mitochondrial disease. The patient's hypo- to hyperphosphatemia in XLH may be mediated by the development of an m.3243A>G-associated nephropathy.
CALCIFIED TISSUE INTERNATIONAL
(2022)
Article
Endocrinology & Metabolism
Inge-Lot Klein, Christianne M. Verhaak, Jan A. M. Smeitink, Paul de Laat, Mirian C. H. Janssen, Jose A. E. Custers
Summary: This study explores the trajectory of fatigue in patients with the mitochondrial DNA 3243 A>G variant over 2 years and finds that severe fatigue is a common and stable symptom in the majority of patients. Patients with a stable high fatigue trajectory show higher disease manifestations, more clinically relevant mental health symptoms, and lower psychosocial functioning and quality of life.
JOURNAL OF INHERITED METABOLIC DISEASE
(2022)
Article
Medicine, General & Internal
Jian-Wei Wang, Xiao-Bo Yuan, Hong-Fang Chen
Summary: In this case report, a unique case of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome initially misdiagnosed as autoimmune encephalitis was ultimately confirmed as MELAS with the mitochondrial DNA 3243A>G mutation.
WORLD JOURNAL OF CLINICAL CASES
(2023)
Review
Genetics & Heredity
Danyang Li, Chunmei Liang, Tao Zhang, Jordan Lee Marley, Weiwei Zou, Muqing Lian, Dongmei Ji
Summary: This review elaborates on the characteristics of the m.3243A > G mutation, from genetics to phenotype and the relationship between them, as well as potential strategies for disease prevention, providing guidance for clinicians providing genetic counseling to m.3243A > G patients.
FRONTIERS IN GENETICS
(2022)
Article
Clinical Neurology
Sjan Teeselink, Sanne C. C. Vincenten, Nicol C. Voermans, Jan T. Groothuis, Jonne Doorduin, Peter J. Wijkstra, Corinne G. C. Horlings, Baziel G. M. van Engelen, Karlien Mul
Summary: The study aimed to evaluate the change in respiratory function in patients with facioscapulohumeral muscular dystrophy (FSHD) over a period of 5 years. The results showed that the respiratory function remained stable in most patients, but a subgroup of patients experienced a significant deterioration. These patients had more severe muscle weakness, spinal and thorax deformities, and a relatively fast decline in axial muscle function over the follow-up period.
JOURNAL OF NEUROLOGY
(2022)
Article
Rehabilitation
Karlien Mul, Feri Wijayanto, Tom G. J. Loonen, Perry Groot, Sanne C. C. Vincenten, Simone Knuijt, Jan T. Groothuis, Thomas J. J. Maal, Tom Heskes, Nicol C. Voermans, Baziel G. M. van Engelen
Summary: This study developed a functional assessment measure for evaluating the functional disabilities associated with facial weakness in facioscapulohumeral muscular dystrophy (FSHD). The measure demonstrated good reliability and validity, and can be used as a tool for further research.
DISABILITY AND REHABILITATION
(2023)
Article
Rehabilitation
Marieke Lindenschot, Saskia Koene, Melissa T. Nott, Maria W. G. Nijhuis-van der Sanden, Imelda J. M. de Groot, Esther M. J. Steultjens, Maud J. L. Graff
Summary: This study investigated the reliability and validity of the PRPP-Assessment using parent-provided videos of children with mitochondrial disorders. The results showed that the PRPP-Assessment demonstrated good psychometric properties in terms of internal consistency, intra-rater reliability, and inter-rater reliability. The PRPP-Assessment also showed good construct validity when compared to the Canadian Occupational Performance Measure. Rasch analysis further supported the validity of the PRPP-Assessment. Therefore, using parent-provided videos for the assessment of the PRPP-Assessment is a feasible approach.
DISABILITY AND REHABILITATION
(2023)
Article
Rehabilitation
W. A. Van de Geest-Buit, N. B. Rasing, K. Mul, J. C. W. Deenen, S. C. C. Vincenten, I Siemann, A. Lanser, J. T. Groothuis, B. G. van Engelen, J. A. E. Custers, N. C. Voermans
Summary: This study aimed to evaluate the psychosocial outcomes of facial weakness in facioscapulohumeral muscular dystrophy (FSHD). The findings showed that patients reported mild to moderate psychological distress, fear of negative evaluation, and social functioning. However, severe self-reported facial weakness was associated with lower social functioning. Patients with more facial dysfunction experienced higher fear of negative evaluation and lower social functioning. Younger age, presence of pain, fatigue, walking difficulty, and psychological support were also factors contributing to lower psychosocial outcomes. Overall, this study suggests that a multidisciplinary, personalized approach is needed to address the physical, emotional, and social consequences of FSHD.
DISABILITY AND REHABILITATION
(2023)
Article
Pediatrics
Marieke Lindenschot, Imelda J. M. de Groot, Maria W. G. Nijhuis-van der Sanden, Esther M. J. Steultjens, Maud J. L. Graff, Saskia Koene
Summary: This study aims to optimize the process of acquiring video material and improve the PRPP-Assessment through parent-provided videos. By conducting five cycles, this study successfully implemented the PRPP-Assessment and learned general lessons on instructing parents, handling video material, and assessing children with limited functional abilities. Lessons learned are recommended to be implemented in practice and included in a manual for video-based observations with PRPP-Assessment.
PHYSICAL & OCCUPATIONAL THERAPY IN PEDIATRICS
(2023)
Review
Clinical Neurology
Karlijn Bouman, Anne T. M. Dittrich, Jan T. Groothuis, Baziel G. M. van Engelen, Mirian C. H. Janssen, Nicol C. Voermans, Jos M. T. Draaisma, Corrie E. Erasmus
Summary: This scoping review summarizes the evidence on bone quality in congenital myopathies and provides recommendations for bone quality management, including bone mineral density assessment, vitamin D and calcium supplementation, and referral to internal medicine or pediatrics for consideration of additional therapies to prevent complications of low bone mineral density.
JOURNAL OF NEUROMUSCULAR DISEASES
(2023)
Article
Clinical Neurology
Renske M. J. Janssen, Renee Lustenhouwer, Edith H. C. Cup, Nens van Alfen, Jos Ijspeert, Rick C. Helmich, Ian G. M. Cameron, Alexander C. H. Geurts, Baziel G. M. van Engelen, Maud J. L. Graff, Jan T. Groothuis
Summary: This study compared the effects of multidisciplinary rehabilitation with usual care on the functional capability of the shoulder, arm, and hand in patients with neuralgic amyotrophy. The results showed that multidisciplinary rehabilitation was more effective in improving shoulder functional capability and reducing pain and fatigue.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Review
Rehabilitation
Nathaniel B. Rasing, Willianne van de Geest-buit, On Ying A. Chan, Karlien Mul, Anke Lanser, Corrie E. Erasmus, Jan T. Groothuis, Judith Holler, Koen J. A. O. Ingels, Bart Post, Ietske Siemann, Nicol C. Voermans
Summary: This study investigates the psychosocial impact of having an altered facial expression in five neurological diseases. The findings show that patients with altered facial expression in four of the diseases had reduced psychosocial functioning. Negative effects were more prevalent in women and more severely affected patients. Future research should examine observers' judgments of patients and the effectiveness of compensation strategies in enhancing psychosocial functioning.
DISABILITY AND REHABILITATION
(2023)
Article
Genetics & Heredity
Loek Crefcoeur, Sacha Ferdinandusse, Saskia N. van der Crabben, Eugenie Dekkers, Sabine A. Fuchs, Hidde Huidekoper, Mirian Janssen, Janneke Langendonk, Rose Maase, Monique de Sain, Estela Rubio, Francjan J. van Spronsen, Frederic Maxime Vaz, Rendelien Verschoof, Maaike de Vries, Frits Wijburg, Gepke Visser, Mirjam Langeveld
Summary: Newborn screening programs can identify various disease phenotypes, leading to the question of whether early identification and treatment is beneficial for all. This study focuses on primary carnitine deficiency (PCD) and found that while most mothers and some newborns with PCD may remain asymptomatic without early treatment, a small proportion of newborns with predicted severe PCD could greatly benefit from early treatment.
JOURNAL OF MEDICAL GENETICS
(2023)
Review
Clinical Neurology
Marloes Middelink, Nicol C. Voermans, Baziel G. M. van Engelen, Mirian C. H. Janssen, Jan T. Groothuis, Simone Knuijt, Heidi Zweers-van Essen
Summary: This study reviewed the indications to start tube feeding in adults with facioscapulohumeral dystrophy, inclusion body myositis, muscular dystrophy type 1, oculopharyngeal muscular dystrophy, and congenital myopathies. The results showed that the indications to start tube feeding were mainly dysphagia, malnutrition/weight loss, and respiratory infections. Percutaneous endoscopic gastrostomy tubes were the most commonly used, but they could cause complications during the process.
JOURNAL OF NEUROMUSCULAR DISEASES
(2023)
Article
Genetics & Heredity
Lisca Florence Wurfbain, Inge Lucia Cox, Maria Francisca van Dooren, Augusta Maria Antonia Lachmeijer, Virginie Johanna Maria Verhoeven, Johanna Maria van Hagen, Malou Heijligers, Jolien Sietske Klein Wassink-Ruiter, Saskia Koene, Saskia Mariska Maas, Hermine Elisabeth Veenstra-Knol, Johannes Kristian Ploos van Amstel, Maarten Pieter Gerrit Massink, Aebele Barber Mink van der Molen, Marie-Jose Henriette van den Boogaard
Summary: NGS-based targeted gene panel testing has high diagnostic yield in CLA/P patients, with 11.3% of patients having pathogenic genetic variants. This study highlights the importance of genetic diagnosis for personalized care and accurate genetic counseling in both isolated and non-familial cases of CLA/P.
MOLECULAR SYNDROMOLOGY
(2023)
Article
Clinical Neurology
Renee Lustenhouwer, Ian G. M. Cameron, Nens van Alfen, Ivan Toni, Alexander C. H. Geurts, Baziel G. M. van Engelen, Jan T. Groothuis, Rick C. Helmich
Summary: This study aimed to determine whether abnormal cerebral sensorimotor representations associated with peripheral nerve damage in neuralgic amyotrophy (NA) can be changed by specialized multidisciplinary outpatient rehabilitation. The results showed that the multidisciplinary rehabilitation group demonstrated significant clinical improvement on the Shoulder Rating Questionnaire, while both groups showed improvement in task performance and increased activity in visuomotor occipito-parietal brain areas specific to the affected upper extremity. This study suggests that abnormal cerebral sensorimotor representations can recover towards normality after peripheral nerve damage.
NEUROREHABILITATION AND NEURAL REPAIR
(2023)
Article
Clinical Neurology
Karlijn Bouman, Jeroen L. M. van Doorn, Jan T. Groothuis, Peter J. Wijkstra, Baziel G. M. van Engelen, Corrie E. Erasmus, Jonne Doorduin, Nicol C. Voermans
Summary: The majority of LAMA2-MD and all SELENON-RM patients had respiratory impairment. SELENON-RM patients showed lower respiratory function which was progressive, more prevalent mechanical ventilation, and more severe diaphragm atrophy and dysfunction than LAMA2-MD patients. Spirometry (FVC%, dVC) and respiratory muscle strength tests (SNIP) are useful in clinical care and as outcome measure in clinical trials.
EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY
(2024)
Article
Pediatrics
Michelle van Slobbe, Arie van Haeringen, Lisenka E. L. M. Vissers, Emilia K. Bijlsma, Julie W. Rutten, Manon Suerink, Esther A. R. Nibbeling, Claudia A. L. Ruivenkamp, Saskia Koene
Summary: This study evaluated the yield of whole-exome sequencing (WES) reanalysis in standard patient care in the Netherlands and found that it significantly increased the genetic diagnosis rate for patients. Most newly diagnosed patients had clinical consequences, and patients with dysmorphic features had a higher diagnostic yield in WES reanalysis.
EUROPEAN JOURNAL OF PEDIATRICS
(2023)
Article
Clinical Neurology
Renee Lustenhouwer, Ian G. M. Cameron, Elze Wolfs, Nens van Alfen, Ivan Toni, Alexander C. H. Geurts, Baziel G. M. van Engelen, Jan T. Groothuis, Rick C. Helmich
Summary: Neuralgic amyotrophy is a common peripheral nerve disorder characterized by pain and weakness in the shoulder muscles. This study reveals that cerebral alterations in visuomotor brain areas contribute to residual motor dysfunction and persistent pain in neuralgic amyotrophy. These findings suggest that targeting visuomotor integration in rehabilitation interventions may help improve sensorimotor function in patients with this condition.
BRAIN COMMUNICATIONS
(2022)
