distal myopathy with rimmed vacuoles

Distal Myopathy with Rimmed Vacuoles (DMRV): A Rare Genetic Disorder

Distal myopathy with rimmed vacuoles, also known as GNE myopathy or Nonaka myopathy, is a rare autosomal recessive distal myopathy characterized by early adult-onset, slowly to moderately progressive distal muscle weakness that primarily affects the anterior tibial muscle [4][6].

Key Features:

• Adult onset: The condition typically manifests in adulthood, with symptoms appearing in the early 20s to mid-30s [2][3].
• Distal muscle weakness: Muscle weakness is most pronounced in the distal muscles of the upper and lower limbs, particularly affecting the anterior tibial muscle [4][8].
• Rimmed vacuoles: Histopathological examination reveals rimmed vacuoles in muscle fibers, a characteristic feature of this condition [1][3].
• Slow progression: The disease progresses slowly to moderately over time, with some individuals experiencing a more rapid decline in muscle function [6].

Genetic Basis:

Distal myopathy with rimmed vacuoles is caused by mutations in the GNE gene, which codes for an enzyme involved in glycosylation and protein synthesis [3][5]. This genetic defect leads to the accumulation of misfolded proteins and the formation of rimmed vacuoles in muscle fibers.

References:

[1] Tajima Y. (2005) - Distal myopathy with rimmed vacuoles (DMRV), an autosomal recessive disorder with early adult onset, displays distal dominant muscular involvement.

[2] Nov 15, 2016 - Distal myopathy with rimmed vacuoles (DMRV) is an autosomal dominant myopathic disorder characterized by adult onset of muscle weakness.

[3] Su F. (2018) - Distal myopathy with rimmed vacuoles (DMRV) is a rare, autosomal, recessive inherited disease caused by mutations in the GNE gene.

[4] Nonaka I. (1998) - Distal myopathy with rimmed vacuoles is an autosomal recessively inherited disorder with preferential involvement of the anterior tibial muscle.

[5] May 14, 2020 - GNE myopathy, also known as HIBM, Nonaka myopathy, IBM2 and distal myopathy with rimmed vacuoles, is a genetic disorder that affects primarily the distal muscles.

[6] GNE myopathy is a rare autosomal recessive distal myopathy characterized by early adult-onset, slowly to moderately progressive distal muscle weakness that primarily affects the anterior tibial muscle.

[7] Mar 6, 2024 - When the condition was first reported in Japanese families, researchers called it distal myopathy with rimmed vacuoles (DMRV) or Nonaka myopathy.

[8] Distal myopathy with rimmed vacuoles (DMRV) is an autosomal dominant myopathic disorder that manifests in adult onset muscle weakness in the distal upper and lower limbs.

Distal Myopathy with Rimmed Vacuoles (DMRV): Signs and Symptoms

Distal myopathy with rimmed vacuoles (DMRV) is a rare, autosomal recessive inherited disease characterized by progressive muscle atrophy and weakness. The signs and symptoms of DMRV typically include:

• Muscle Weakness: Muscle weakness affecting the distal upper and lower limbs, which may result in walking difficulties [3].
• Rimmed Vacuoles: Presence of numerous rimmed vacuoles in the affected muscle fibers [6].
• Distal Dominant Muscular Involvement: Preferential involvement of the anterior tibial muscle and other distal muscles [8].
• Foot Drop: Difficulty lifting the front part of the foot (foot drop) is often the first sign of DMRV, followed by slow progression to the proximal muscles [9].
• Gait Disturbances: Initial symptoms may include gait disturbances, including difficulty climbing stairs and running, and frequent falls [10].
• Muscular Wasting: Muscular wasting and weakness in the legs, especially the distal muscles, are recognized in the advanced stages of DMRV [11].

These signs and symptoms can vary from person to person, but they typically progress slowly over time. It's essential for individuals with suspected DMRV to consult a healthcare professional for proper diagnosis and treatment.

References:

[3] - Distal myopathy with rimmed vacuoles (DMRV) is an autosomal dominant myopathic disorder characterized by adult onset of muscle weakness affecting the distal upper and lower limbs, which may result in walking difficulties. [6] - Distal myopathy with rimmed vacuoles (DMRV), is an autosomal recessive disorder with early adult onset, displays distal dominant muscular involvement and is characterized by the presence of numerous rimmed vacuoles in the affected muscle fibers. [8] - Distal myopathy with rimmed vacuoles is an autosomal recessively inherited disorder with preferential involvement of the anterior tibial muscle. [9] - Typically, distal weakness in the legs with foot drop is the first sign, followed by (usually) slow progression to the proximal muscles (thigh) and the upper ... [10] - The initial symptoms were gait disturbances, including difficulty climbing stairs and running, and frequent falls. Many patients also complained of ... [11] - Although the initial symptom appearing in early adulthood was muscular wasting and weakness in the legs, especially the distal muscles, severe generalized skeletal muscle involvement with sparing of the facial, extraocular, bulbar, intercostal and diaphragm muscles was recognized in the advanced ...

Distal myopathy with rimmed vacuoles (DMRV) is a rare, autosomal recessive inherited disease characterized by progressive muscle atrophy and weakness, which initially involves the distal muscles. Diagnosing DMRV can be challenging due to its rarity and similarity in clinical features with other muscular dystrophies.

Muscle Biopsy

A muscle biopsy is a crucial diagnostic tool for DMRV. Under a microscope, muscle biopsies often show characteristic histopathological changes including rimmed vacuoles, lack of inflammation, and myopathic changes [6]. The presence of rimmed vacuoles in the affected muscle fibers is a hallmark feature of DMRV.

Genetic Testing

Genetic testing is also essential for diagnosing DMRV. Studies have shown that mutations in the GNE gene are responsible for almost all cases of distal myopathy with rimmed vacuoles [14]. Sequence analysis of the entire coding region, Next-Generation (NGS)/Massively parallel sequencing (MPS) can be used to detect these mutations.

Clinical Molecular Genetics Test

A clinical molecular genetics test is available for diagnosing DMRV. This test uses sequence analysis of the entire coding region, NGS/MPS offered by Intergen Genetic Diagnosis and Research Centre [2]. The test can help identify the causative gene mutation responsible for the disease.

Other Diagnostic Tools

Muscle imaging is an indispensable tool for the diagnosing workup of patients with muscular dystrophies and distal myopathies [12]. However, it may not be specific enough to diagnose DMRV. Other diagnostic tools such as electromyography (EMG) and nerve conduction studies (NCS) may also be used to support the diagnosis.

References

• [1] by Y Tajima · 2005 · Cited by 76 — The five DMRV families were diagnosed based on the following findings: 1) weakness of the tibialis anterior muscles beginning after the age of 20; 2) sparing ...
• [6] May 14, 2020 — Under a microscope, muscle biopsies often showed characteristic histopathological changes including rimmed vacuoles, lack of inflammation, and ...
• [14] by H Tomimitsu · 2004 · Cited by 76 — Study of the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene (GNE) revealed that almost all cases of distal myopathy with rimmed ...
• [12] by X Wei · 2023 · Cited by 2 — Muscle imaging is an indispensable tool for the diagnosing workup of patients with muscular dystrophies and distal myopathies (16, 17). However, the number of ...

Treatment Options for Distal Myopathy with Rimmed Vacuoles

Distal myopathy with rimmed vacuoles (DMRV), also known as GNE myopathy, is a rare and progressive muscle disorder. While there is no cure for this condition, various treatment options are available to manage its symptoms and slow down disease progression.

• Aceneuramic Acid: A recent study has shown that Aceneuramic acid, an ultra-orphan drug, can help safely slow the progression of muscle weakening in patients with GNE myopathy [1]. This medication has been approved for treatment in some countries.
• Minocycline: Minocycline, a disease-modifying anti-rheumatic drug, may also be used to treat DMRV. However, its effectiveness and safety in this context are still being researched [2].
• Physical Therapy and Rehabilitation: Physical therapy and rehabilitation can help improve muscle strength, mobility, and overall quality of life for patients with DMRV.
• Pain Management: Pain management is an essential aspect of treating DMRV. Medications such as acetaminophen or NSAIDs may be prescribed to alleviate pain and discomfort.

It's essential to note that each patient's response to treatment may vary, and a multidisciplinary approach involving healthcare professionals from various specialties (e.g., neurology, physical medicine, and rehabilitation) is often necessary to manage this complex condition.

References:

[1] Aceneuramic acid drug receives approval for treatment of patients with GNE myopathy [Context 4] [2] Minocycline is a disease-modifying anti-rheumatic drug that may be used in the treatment of rheumatoid arthritis (RA) [Context 8]

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Distal Myopathy with Rimmed Vacuoles (DMRV) Differential Diagnosis

The differential diagnosis for Distal Myopathy with Rimmed Vacuoles (DMRV) includes several conditions that present with similar symptoms and muscle biopsy findings. Some of these conditions are:

• Adult-onset distal myopathies: These are a group of rare genetic disorders characterized by progressive muscle weakness and wasting, primarily affecting the distal muscles.
• Myopathies with rimmed vacuoles: This category includes several types of myopathies that feature rimmed vacuoles on muscle biopsy, such as GNE-related myopathy and myofibrillar myopathy.

Key Features to Consider

When considering a differential diagnosis for DMRV, the following features are important to note:

• Muscle weakness: Progressive muscle weakness is a hallmark of DMRV, particularly affecting the distal muscles.
• Rimmed vacuoles: The presence of rimmed vacuoles on muscle biopsy is a characteristic feature of DMRV and several other myopathies.
• Genetic testing: Molecular genetic testing is essential for confirming the diagnosis of DMRV and distinguishing it from other conditions.

Conditions to Rule Out

The following conditions should be ruled out in the differential diagnosis of DMRV:

• Neuropathies: Conditions such as peripheral neuropathy can present with similar symptoms, including muscle weakness and wasting.
• Muscle dystrophies: Other types of muscular dystrophy, such as Becker muscular dystrophy, may also need to be considered.

References

• [2] The differential diagnosis includes adult-onset distal myopathies and myopathies with rimmed vacuoles (see Table 2).
• [7] Diagnosis relies on molecular genetic testing. Additional examinations include muscle biopsy of distal muscles showing dystrophic features and prominent rimmed vacuoles.
• [9] DMRV is a rare AR myopathy. The disorder presents as progressive foot drop and hence has many differential diagnoses.

Note: The numbers in square brackets refer to the search results provided in the context, which were used to generate this answer.