Muscle disorders P-MU002. Mutation spectrum of congenital muscular dystrophies: A case series from India

Muscular dystrophies (MDs) are a group of inherited degenerative muscle disorders characterized by a progressive skeletal muscle wasting. Respiratory impairments and subsequent hypoxemia are encountered in a significant subgroup of patients in almost all MD forms. In response to hypoxic stress, compensatory mechanisms are activated especially through Hypoxia-Inducible Factor 1 α (HIF-1α). In healthy muscle, hypoxia and HIF-1α activation are known to affect oxidative stress balance and metabolism. Recent evidence has also highlighted HIF-1α as a regulator of myogenesis and satellite cell function. However, the impact of HIF-1α pathway modifications in MDs remains to be investigated. Multifactorial pathological mechanisms could lead to HIF-1α activation in patient skeletal muscles. In addition to the genetic defect per se, respiratory failure or blood vessel alterations could modify hypoxia response pathways. Here, we will discuss the current knowledge about the hypoxia response pathway alterations in MDs and address whether such changes could influence MD pathophysiology.

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Congenital muscular dystrophies: New evidence-based guidelines for the diagnosis and management of this evolving group of muscle disorders

Muscle & Nerve ◽

10.1002/mus.24683 ◽

2015 ◽

Vol 51 (6) ◽

pp. 791-792 ◽

Cited By ~ 1

Author(s):

Hugh J. McMillan

Keyword(s):

Muscular Dystrophies ◽

Evidence Based ◽

Muscle Disorders ◽

Diagnosis And Management ◽

Evidence Based Guidelines ◽

New Evidence

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Inherited Muscle Disorders

10.1093/med/9780197512166.003.0090 ◽

2021 ◽

pp. 785-797

Author(s):

Teerin Liewluck ◽

Margherita Milone

Keyword(s):

Extracellular Matrix ◽

Matrix Proteins ◽

Muscle Membrane ◽

Muscular Dystrophies ◽

Collagen Vi ◽

Membrane Protein Complex ◽

Muscle Disorders ◽

Progressive Degeneration ◽

Muscular Disorders ◽

Intracellular Proteins

Inherited muscular disorders can manifest at any age, from prenatal life to adulthood. The broad differential diagnosis includes muscular dystrophies, congenital myopathies, disorders of glycogen and lipid metabolism, channelopathies, and mitochondrial disorders. Muscular dystrophies may present at any age, are inherited, and involve progressive degeneration of muscle, which is often replaced by connective tissue. Muscular dystrophies result from defects in the sarcolemmal proteins of muscle, including dystrophin-associated muscle membrane protein complex, muscle intracellular proteins (eg, nuclear envelope proteins), and extracellular matrix proteins (eg, collagen VI).

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A pilot case series of a brief acceptance and commitment therapy (ACT)-based guided self-help intervention for improving quality of life and mood in muscle disorders

The Cognitive Behaviour Therapist ◽

10.1017/s1754470x17000022 ◽

2017 ◽

Vol 10 ◽

Cited By ~ 2

Author(s):

Christopher D. Graham ◽

Trudie Chalder ◽

Michael R. Rose ◽

Dimitri Gavriloff ◽

Lance M. McCracken ◽

...

Keyword(s):

Quality Of Life ◽

Acceptance And Commitment Therapy ◽

Case Series ◽

Psychological Flexibility ◽

Secondary Outcome ◽

Muscle Disorders ◽

Self Help ◽

Commitment Therapy ◽

Acceptance And Commitment

AbstractThis study aimed to demonstrate proof of concept and acceptability of a brief acceptance and commitment therapy (ACT)-based guided self-help intervention for improving quality of life (QoL) and mood for people with muscle disorders (MD). A case-series with an AB design was used to assess changes in primary (QoL) and secondary (depression and anxiety) outcome variables across the period of study. Change in the psychological process targeted by ACT – psychological flexibility – was also investigated, to allow insight into possible treatment mechanisms. Post-intervention, participants also completed a brief free-text evaluation. Relative to pre-intervention scores, four (of seven) participants showed varying degrees of improvement in all primary and secondary outcome variables and were thus considered responders. However, consistent concomitant improvements in psychological flexibility were not apparent. Participants reported a mostly positive experience of the intervention; all appeared to complete the intervention, and no adverse events were reported. Nonetheless, there was evidence that those with compromised concentration or who report good initial QoL and low levels of distress may derive less benefit. Although several methodological weaknesses limit the strength of our conclusions, this ACT-based guided self-help intervention shows encouraging utility for improving QoL and mood in MD.

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Redox Homeostasis in Muscular Dystrophies

Cells ◽

10.3390/cells10061364 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1364

Author(s):

Nicola Mosca ◽

Sara Petrillo ◽

Sara Bortolani ◽

Mauro Monforte ◽

Enzo Ricci ◽

...

Keyword(s):

Oxidative Stress ◽

Protein Function ◽

Cell Damage ◽

Redox Homeostasis ◽

Muscular Dystrophies ◽

Dna Integrity ◽

Muscle Disorders ◽

Structure Lipid ◽

Muscle Homeostasis

In recent years, growing evidence has suggested a prominent role of oxidative stress in the pathophysiology of several early- and adult-onset muscle disorders, although effective antioxidant treatments are still lacking. Oxidative stress causes cell damage by affecting protein function, membrane structure, lipid metabolism, and DNA integrity, thus interfering with skeletal muscle homeostasis and functionality. Some features related to oxidative stress, such as chronic inflammation, defective regeneration, and mitochondrial damage are shared among most muscular dystrophies, and Nrf2 has been shown to be a central player in antagonizing redox imbalance in several of these disorders. However, the exact mechanisms leading to overproduction of reactive oxygen species and deregulation in the cellular antioxidants system seem to be, to a large extent, disease-specific, and the clarification of these mechanisms in vivo in humans is the cornerstone for the development of targeted antioxidant therapies, which will require testing in appropriately designed clinical trials.

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THREE CASE SERIES INVOLVING PROGRESIVE MOTOR DEFICIT

Romanian Journal of Neurology ◽

10.37897/rjn.2016.4.7 ◽

2016 ◽

Vol 15 (4) ◽

pp. 183-186

Author(s):

Bogdan Pana ◽

◽

Alina Anghel ◽

Iuliana Nicola-Antoniu ◽

Ioan Buraga ◽

...

Keyword(s):

Clinical Trials ◽

Muscular Dystrophy ◽

Muscle Wasting ◽

Case Series ◽

Motor Deficit ◽

Muscular Dystrophies ◽

The Third ◽

First Case ◽

Family Medical History ◽

Pelvic Muscles

The muscular dystrophies are a group of inherited, non-inflammatory disorders, consisting of progressive muscle wasting, without peripheral or central nerve involvement. We present a series of three cases involving progressive motor deficit and their different evolutions. The first case is about a 57 year old female patient, without a significant family medical history, presenting for progressive motor deficit involving the shoulder and pelvic muscles, started at the age of 20 year old, when she was diagnosed with a sporadic form of limb-girdle muscular dystrophy. The second case is about a 27 year old male, diagnosed with muscular dystrophy at the age of 15. The third case is about a 43 year old male admitted for frequent falls and weakness of the limbs, mainly distal, started 10 years ago. He was diagnosed with myotonic dystrophy. Although there is still no treatment for muscular dystrophies, the pathology is under investigation in clinical trials.

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Mutation spectrum of MMACHC in Chinese pediatric patients with cobalamin C disease: A case series and literature review

European Journal of Medical Genetics ◽

10.1016/j.ejmg.2019.103713 ◽

2019 ◽

Vol 62 (10) ◽

pp. 103713 ◽

Cited By ~ 5

Author(s):

Chao Wang ◽

Dong Li ◽

Fengying Cai ◽

Xinjie Zhang ◽

Xiaowei Xu ◽

...

Keyword(s):

Literature Review ◽

Pediatric Patients ◽

Case Series ◽

Mutation Spectrum

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Unmet needs and evolving treatment for limb girdle muscular dystrophies

Neurodegenerative Disease Management ◽

10.2217/nmt-2020-0066 ◽

2021 ◽

Author(s):

Eric Pozsgai ◽

Danielle Griffin ◽

Rachael Potter ◽

Zarife Sahenk ◽

Kelly Lehman ◽

...

Keyword(s):

Gene Therapy ◽

Clinical Trials ◽

Experimental Studies ◽

Muscular Dystrophies ◽

Muscle Disorders ◽

Autosomal Recessive Disorders ◽

Recessive Disorders ◽

Single Dosing ◽

Made In

Limb-girdle muscular dystrophies (LGMDs) represent a major group of muscle disorders. Treatment is sorely needed and currently expanding based on safety and efficacy adopting principles of single-dosing gene therapy for monogenic autosomal recessive disorders. Gene therapy has made in-roads for LGMD and this review describes progress that has been achieved for these conditions. This review first provides a background on the definition and classification of LGMDs. The major effort focuses on progress in LGMD gene therapy, from experimental studies to clinical trials. The disorders discussed include the LGMDs where the most work has been done including calpainopathies (LGMD2A/R1), dysferlinopathies (LGMD2B/R2) and sarcoglycanopathies (LGMD2C/R5, LGMD2D/R3, LGMD2E/R4). Early success in clinical trials provides a template to move the field forward and potentially apply emerging technology like CRISPR/Cas9 that may enhance the scope and efficacy of gene therapy applied to patient care.

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