autosomal recessive limb-girdle muscular dystrophy

Autosomal Recessive Limb-Girdle Muscular Dystrophy (LGMDR) refers to a group of rare genetic disorders that affect the muscles around the shoulders and hips, leading to progressive muscle weakness and wasting.

• Characteristics: LGMDR is characterized by childhood-onset of proximal muscle weakness resulting in gait disturbances [4]. The age at onset varies, but most cases are diagnosed in early childhood [8].
• Symptoms: Affected individuals may experience difficulty walking, running, or climbing stairs due to weakness and wasting of the proximal muscles [8].
• Inheritance pattern: LGMDR is inherited in an autosomal recessive pattern, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition [3].

It's worth noting that LGMD can be divided into two main forms: Autosomal Dominant (LGMD D) and Autosomal Recessive (LGMD R), with LGMDR being one of the many subtypes of the latter [9].

Major Clinical Features

Autosomal recessive limb-girdle muscular dystrophy (LGMD) is characterized by progressive weakness and muscle atrophy mainly involving the shoulder girdle, also known as scapulohumeral type. This condition affects the muscles in the arms and legs, leading to a range of symptoms.

Common Symptoms

• Muscle weakness and atrophy in the shoulders, upper arms, hips, and pelvic region [1]
• Progressive muscle weakness that may spread to affect other muscles in the body [3]
• Frequent falls due to weakness in the big muscles of the legs and/or arms [7]
• Difficulty running, climbing stairs, or getting up from the floor [5]

Additional Symptoms

• Joint stiffness
• Muscle cramps
• Enlargement of calf muscles (in some subtypes)
• Pelvic muscle weakness, including trouble standing from a sitting position without using the arms [8]

Progression and Age of Onset

The age of onset can vary, but general signs and symptoms of LGMD include progressive weakness and muscle atrophy involving the shoulders, pelvic girdle, or both. The condition typically affects individuals in their childhood to early adulthood, with some cases reported in older adults [9].

References

[1] Signs and Symptoms ... Major clinical features of LGMDs are progressive weakness and muscle atrophy mainly involving the shoulder girdle (scapulohumeral type), ... [3] Oct 1, 2019 — Muscle weakness and atrophy are progressive and may spread to affect other muscles of the body. Many different subtypes have been identified ... [5] Apr 12, 2023 — Symptoms of limb girdle muscular dystrophy · frequent falls · difficulty running · difficulty climbing stairs · difficulty getting up from the floor ... [7] However, the common features to all people in this group will be weakness of the big muscles of the legs and/or arms. This may result in frequent falls, ... [8] Dec 31, 2023 — Most often, the first sign is pelvic muscle weakness. Examples of this include trouble standing from a sitting position without using the arms, ... [9] Aug 14, 2024 — General signs and symptoms of LGMD include progressive weakness and muscle atrophy involving the shoulders, pelvic girdle, or both. The age of ...

Autosomal recessive limb-girdle muscular dystrophy (LGMD) can be diagnosed through various tests, including:

• Creatine kinase blood test: This test measures the level of creatine kinase in the blood. In LGMD, this enzyme is often elevated, especially in autosomal recessive forms [2].
• Muscle biopsies: A muscle biopsy involves taking a small sample of muscle tissue from the affected area. This can help confirm the diagnosis and identify the specific subtype of LGMD [8].
• Genetic testing: Genetic testing can be used to identify mutations in the genes associated with LGMD, such as ANO5 or BVES [5]. This can help confirm the diagnosis and provide information on the inheritance pattern.
• Blood tests: Blood tests may also be performed to rule out other conditions that may cause similar symptoms. For example, a creatine kinase blood test can help differentiate between autosomal dominant and autosomal recessive forms of LGMD [2].
• Imaging studies: Imaging studies such as computed tomography (CT) scans or magnetic resonance imaging (MRI) may be used to assess muscle damage and confirm the diagnosis.

It's worth noting that a combination of clinical assessment, specialized muscle immunoanalysis, and genetic testing is often necessary to diagnose LGMD accurately [7].

Current Status of Drug Treatment for Autosomal Recessive Limb-Girdle Muscular Dystrophy

Unfortunately, there is no specific treatment available for any of the LGMD syndromes, including autosomal recessive limb-girdle muscular dystrophy (LGMD2) [4]. However, aggressive supportive care is essential to manage symptoms and prevent complications.

Emerging Therapies

Recent research has focused on gene therapy as a potential treatment approach for LGMDs. Gene therapy involves introducing a healthy copy of the faulty gene into cells to replace the defective one. This approach has shown promise in treating monogenic autosomal recessive disorders, including some forms of LGMD [14].

Clinical Trials

A clinical trial is currently underway to test the safety and efficacy of a treatment for LGMD2, which includes autosomal recessive limb-girdle muscular dystrophy [12]. The primary goal of this trial is to determine the incidence of adverse events after dosing, with participants being followed for an additional 4.5 years.

Future Directions

While there are no approved treatments available for autosomal recessive limb-girdle muscular dystrophy, ongoing research efforts aim to conquer this group of genetic neuromuscular diseases. Continued investigation into gene therapy and other emerging therapies may lead to the development of effective treatments in the future.

References:

[4] Aug 15, 2019 — No specific treatment is available for any of the LGMD syndromes, though aggressive supportive care is essential. [12] Trial will be 1st to test treatment for this limb-girdle muscular dystrophy type. [14] Gene therapy has made in-roads for LGMD …

Differential Diagnosis of Autosomal Recessive Limb-Girdle Muscular Dystrophy

Autosomal recessive limb-girdle muscular dystrophy (LGMD) is a group of disorders that cause weakness and wasting of the muscles in the arms and legs. The differential diagnosis of LGMD involves distinguishing it from other myopathies, such as Duchenne and Becker muscular dystrophy, Emery-Dreifuss muscular dystrophy, and others.

Key Features to Consider

• Age of onset: Autosomal recessive LGMD typically presents in childhood or adolescence.
• Muscle distribution: The disease primarily affects the proximal muscles of the limbs.
• Creatine kinase levels: Elevated creatine kinase levels are often seen in autosomal recessive LGMD, particularly compared to autosomal dominant forms.

Differential Diagnosis Considerations

• Duchenne and Becker muscular dystrophy: These conditions also present with muscle weakness and wasting, but typically have a later age of onset and different genetic etiology.
• Emery-Dreifuss muscular dystrophy: This condition is characterized by early contractures and muscle weakness, often with a more severe course than autosomal recessive LGMD.

Genetic Considerations

• Sarcoglycan mutations: Mutations in genes encoding sarcoglycans are associated with autosomal recessive LGMD.
• Dystroglycan mutations: Mutations in the POMT1 gene, which encodes a component of dystroglycan, have been linked to autosomal recessive LGMD.

Clinical and Laboratory Features

• Muscle biopsy: A muscle biopsy can help confirm the diagnosis by showing characteristic features such as muscle fiber degeneration and regeneration.
• Imaging studies: Imaging studies like MRI or CT scans may show muscle atrophy and weakness, particularly in the proximal muscles of the limbs.

References

• [3] Limb-girdle muscular dystrophy is a term for a group of diseases that cause weakness and wasting of the muscles in the arms and legs.
• [4] Oct 1, 2019 — These disorders can now be distinguished by genetic and protein analysis. The various forms of LGMD may be inherited as autosomal dominant or ...
• [5] Limb-girdle muscular dystrophy (LGMD) is a group of myopathies that lead to progressive muscle weakness, predominantly involving the shoulder and pelvic girdles; it has a heterogeneous genetic etiology, with variation in the prevalence of subtypes according to the ethnic backgrounds and geographic origins of the populations.
• [13] Frequency of autosomal recessive limb girdle muscular dystrophy subtypes in Japan. LGMD-R2 (dysferlin-related LGMD) and LGMD-R1 (calpain 3-related LGMD) are the most common LGMD subtypes in Japan.

Note: The references provided are a selection from the search results and are intended to support the information presented above.