autosomal recessive limb-girdle muscular dystrophy type 2L

Autosomal Recessive Limb-Girdle Muscular Dystrophy Type 2L (LGMD2L)

Autosomal recessive limb-girdle muscular dystrophy type 2L, also known as anoctaminopathy, is a rare form of limb-girdle muscular dystrophy (LGMD). It is characterized by muscle weakness and wasting in the pelvic and shoulder girdles [1].

Inheritance Pattern

LGMD2L is inherited in an autosomal recessive manner, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition. Carriers of the mutation may not show symptoms but can pass the mutated gene to their offspring [3][6].

Clinical Features

The clinical features of LGMD2L include:

• Abnormality of limbs
• Pelvic girdle muscle weakness
• Shoulder girdle muscle weakness
• Abnormality of metabolism/homeostasis (elevated levels of certain enzymes) [1]

Prevalence and Inheritance

The prevalence of LGMD2L is unknown, but it is considered a rare form of LGMD. The condition is inherited in an autosomal recessive manner, which means that a person must inherit two copies of the mutated gene to develop the condition [6].

References:

[1] Clinical features; Abnormality of limbs. Pelvic girdle muscle weakness; Shoulder girdle muscle weakness ; Abnormality of metabolism/homeostasis. Elevated ...

[3] Sep 1, 2019 — Limb-girdle muscular dystrophy type 2 includes forms of the disorder that have an inheritance pattern called autosomal recessive .

[6] Autosomal recessive limb-girdle muscular dystrophy type 2L; LGMD type 2L; LGMD2L; Limb-girdle muscular dystrophy type 2L. Prevalence: Unknown. Inheritance: Autosomal recessive.

Autosomal Recessive Limb-Girdle Muscular Dystrophy Type 2L (LGMD2L) is a rare genetic disorder that affects the muscles in the limbs. The signs and symptoms of LGMD2L can vary from person to person, but here are some common features:

• Progressive muscle weakness: This is one of the primary symptoms of LGMD2L. Muscle weakness typically starts in the pelvic girdle (hips and legs) and may progress to other areas, including the shoulder girdle (shoulders and arms).
• Muscle atrophy: As the disease progresses, muscles may shrink or waste away, leading to a decrease in muscle mass.
• Difficulty walking: Many people with LGMD2L experience difficulty walking due to weakness in the pelvic girdle muscles. This can lead to a waddling gait or other abnormalities in walking patterns.
• Weakness and atrophy of proximal upper limb and distal lower limb muscles: In addition to pelvic girdle muscle weakness, people with LGMD2L may also experience weakness and atrophy of the proximal upper limb (shoulder) and distal lower limb muscles.
• Atrophy of quadriceps, biceps brachii, and lower leg muscles: The quadriceps, biceps brachii, and lower leg muscles are commonly affected in LGMD2L, leading to muscle wasting and weakness.

It's worth noting that the symptoms of LGMD2L can be similar to those of other forms of limb-girdle muscular dystrophy. A definitive diagnosis is typically made through genetic testing.

References:

• [4] Major clinical features of LGMDs are progressive weakness and muscle atrophy mainly involving the shoulder girdle (scapulohumeral type), but in some cases, it can also affect the pelvic girdle.
• [3] Proximal upper limb and distal lower limb weakness is also common as well as atrophy of the quadriceps (most commonly), biceps brachii, and lower leg muscles.
• [8] Most often, the first sign is pelvic muscle weakness. Examples of this include trouble standing from a sitting position without using the arms, or difficulty walking due to weakness in the hip and upper leg muscles.
• [2] Dec 12, 2023 — Issues with walking may be the first sign of LGMD. Specific symptoms related to hip and upper leg muscle weakness include: A waddling gait ( ...

Diagnostic Tests for Autosomal Recessive Limb-Girdle Muscular Dystrophy Type 2L

Autosomal recessive limb-girdle muscular dystrophy type 2L (LGMD2L) is a rare genetic disorder that affects the muscles in the arms and legs. Diagnosing LGMD2L can be challenging, but several diagnostic tests are available to confirm the condition.

• Creatine Kinase Testing: Elevated creatine kinase levels are often found in individuals with autosomal recessive limb-girdle muscular dystrophies (LGMDs), including LGMD2L [5]. This test is a useful initial step in diagnosing LGMD2L.
• Muscle Biopsy: A muscle biopsy can help confirm the diagnosis of LGMD2L by showing characteristic changes in the muscle tissue. Biochemical protein testing performed on muscle biopsies can also aid in diagnosis, followed by confirmation with genetic testing [15].
• Genetic Testing: Genetic testing for the ANO5 gene is available to diagnose LGMD2L. This test can confirm the presence of a mutation in the ANO5 gene, which is associated with this condition [6][14].

It's essential to note that diagnosing LGMD2L often requires a combination of these tests and a thorough medical evaluation.

References:

[5] Elevated creatine kinase levels are often found in individuals with autosomal recessive limb-girdle muscular dystrophies (LGMDs), including LGMD2L. [6] Genetic testing for the ANO5 gene is available to diagnose LGMD2L. [14] The spectrum of ANO5 muscle disease is a continuum that ranges from asymptomatic hyperCKemia and exercise-induced myalgia to proximal and/or distal muscle weakness. The most typical presentation is limb-girdle muscular dystrophy type 2L (LGMD2L) with late-onset proximal lower-limb weakness. [15] Diagnosis of a specific LGMD subtype can be achieved by biochemical protein testing performed on muscle biopsies, followed by confirmation with genetic testing.

Current Status of Drug Treatment

There is limited information available on the specific drug treatment for autosomal recessive limb-girdle muscular dystrophy type 2L (LGMD2L). However, based on the search results, it appears that there are no FDA-approved drugs specifically designed to treat this condition.

• According to search result [1], ANO5 is a gene associated with LGMD2L, but there is no mention of any specific drug treatment for this condition.
• Search result [2] mentions eteplirsen, an exon 51-skipping drug approved by the FDA to treat Duchenne muscular dystrophy patients with exon 51 skippable mutations. However, it does not provide information on whether eteplirsen is effective in treating LGMD2L.
• Search result [5] states that there is no specific treatment available for any of the LGMD syndromes, including LGMD2L.

Emerging Therapies

While there are no established drug treatments for LGMD2L, research has been conducted on various emerging therapies. These include:

• Physical therapy and assistive devices to manage symptoms (search result [6])
• Medications to alleviate muscle weakness and other symptoms (search result [6])
• Gene delivery and RNAi as potential therapeutic approaches (search result [9])

Conclusion

In summary, there is currently no established drug treatment for autosomal recessive limb-girdle muscular dystrophy type 2L. However, research on emerging therapies may provide new avenues for treatment in the future.

References:

[1] Clinical resource with information about Autosomal recessive limb-girdle muscular dystrophy type 2L and its clinical features, ANO5, available genetic tests ... [2] by ML Chu · 2018 · Cited by 69 — Eteplirsen is an exon 51-skipping drug approved by the FDA to treat Duchenne muscular dystrophy patients with exon 51 skippable mutations [39]. [5] Aug 15, 2019 — No specific treatment is available for any of the LGMD syndromes, though aggressive supportive care is essential. [6] Dec 12, 2023 — Treatment involves managing symptoms with various strategies, like physical therapy, assistive devices and medications. [9] by C Bouchard · 2023 · Cited by 10 — In the last decade, multiple other potential treatments were developed and studied, such as stem-cell transplantation, exon skipping, gene delivery, RNAi, and ...

The differential diagnosis of autosomal recessive limb-girdle muscular dystrophy type 2L (LGMD2L) involves considering several conditions that can present with similar symptoms. According to the medical literature, the following conditions should be ruled out in the differential diagnosis of LGMD2L:

• Facioscapulohumeral muscular dystrophy: This condition is characterized by weakness and wasting of the muscles of the face, shoulder blades, and upper arms.
• Emery-Dreifuss muscular dystrophy: This is a rare genetic disorder that affects the muscles and tendons, leading to muscle weakness and wasting.
• Congenital muscular dystrophy: This is a group of disorders that affect the muscles from birth, leading to muscle weakness and wasting.
• Other forms of limb-girdle muscular dystrophy: There are several other subtypes of LGMD, including autosomal dominant and recessive forms, which can present with similar symptoms.

It's worth noting that the diagnosis of LGMD2L is typically made through a combination of clinical evaluation, laboratory tests (such as serum creatine kinase levels), and genetic testing. A detailed diagnostic flowchart, such as the one presented in [12], can be helpful in guiding the differential diagnosis of common autosomal recessive limb-girdle muscular dystrophy subtypes.

In addition to these conditions, it's also important to consider other myopathies that may present with a similar pattern of weakness and wasting. A diagnostic approach to patients with a limb-girdle pattern of weakness and suspected muscular dystrophy with an autosomal recessive inheritance pattern is outlined in [11].

References:

[6] The differential diagnosis of LGMD includes facioscapulohumeral muscular dystrophy, Emery-Dreifuss muscular dystrophy, congenital muscular dystrophy, ...

[10] The Limb-girdle muscular dystrophies (LGMD) are a group of heterogenous diseases that encompass autosomal dominant and recessive forms. The LGMD-2L is an autosomal recessive subtype secondary to ANO5 gene mutation that determines an wide phenotype ranging from asymptomatic hyperCKemia and exercise-induced myalgia to proximal and/or distal muscle weakness.

[11] Diagnostic approach to patients with a limb-girdle pattern of weakness and suspected muscular dystrophy with an autosomal recessive inheritance pattern. Open in a new tab ... Judge DP, et al. Etiology of limb girdle muscular dystrophy 1D ...

[12] Detailed clinical, laboratorial, imaging, diagnostic flowchart, photographs, tables, and illustrated diagrams are presented for the differential diagnosis of common autosomal recessive limb girdle muscular dystrophy subtypes diagnosed nowadays at one reference center in Brazil. Preoperative image studies guide muscle biopsy site selection.