autosomal recessive limb-girdle muscular dystrophy type 2U

Autosomal recessive limb-girdle muscular dystrophy type 2U, also known as LGMD2U or ISPD-related muscular dystrophy, is a rare subtype of autosomal recessive limb-girdle muscular dystrophy.

Characteristics:

• This condition is caused by mutations in the ISPD gene.
• It is characterized by infantile to childhood-onset of slowly progressive muscle weakness and wasting, primarily affecting the proximal muscles of the limbs (shoulders and hips).
• The symptoms can be similar to those of other forms of LGMD, but the specific genetic cause sets it apart.

Inheritance pattern:

• Autosomal recessive inheritance means that an individual must inherit two copies of the mutated gene (one from each parent) to express the condition.
• Carriers of the mutation may not show symptoms themselves but can pass the mutated gene to their offspring.

Other forms of LGMD:

• It's worth noting that there are several other subtypes of autosomal recessive limb-girdle muscular dystrophy, including LGMD2B and distal muscular dystrophy of Miyoshi (MM), which have different genetic causes and clinical features.

References:

• [8] Mutations in human and/or mouse homologs are associated with this disease. Synonyms: autosomal recessive limb-girdle muscular dystrophy due to ISPD ...
• [9] Synonyms: autosomal recessive limb-girdle muscular dystrophy due to ISPD deficiency; LGMD2U; MDDGC7; muscular dystrophy limb-girdle type 2U ...

Autosomal recessive limb-girdle muscular dystrophy (LGMD) type 2U is a rare subtype of LGMD characterized by infantile to childhood-onset of slowly progressive, principally distal muscle weakness. The signs and symptoms of this condition may include:

• Pelvic muscle weakness: This is often the first symptom to occur.
• Asymmetric or distal weakness: This can be a feature in some cases, although it's considered rare.
• Proximal weakness in the lower extremities: Difficulty walking and a positive Gowers sign are usually noted.
• Difficulty walking: Due to muscle weakness, individuals with LGMD type 2U may experience difficulty walking or maintaining balance.
• Muscle cramps: Joint stiffness and muscle cramps can also be present in some cases.

It's essential to note that the symptoms of autosomal recessive LGMD type 2U can vary in severity and progression. The condition is often associated with mildly elevated creatine kinase (CK) levels, which can indicate muscle damage.

References:

• [6] Pelvic muscle weakness is most often the first symptom.
• [7] Common, childhood to young adult onset, moderate to severe weakness, mild to highly elevated CK, common exercise intolerance.
• [8] Proximal weakness in the lower extremities, difficulty walking, and a positive Gowers sign are usually noted.
• [9] Clinical signs and symptoms observed in autosomal recessive limb-girdle muscular dystrophy type 2U.

Autosomal recessive limb-girdle muscular dystrophy type 2U (LGMD2U) is a rare subtype of LGMD, and its diagnosis can be challenging. However, several diagnostic tests are available to confirm the presence of this condition.

Genetic Testing The most accurate method for diagnosing LGMD2U is genetic testing. This involves analyzing the DNA sequence of the ISPD gene, which is responsible for encoding the protein involved in this subtype of LGMD [5]. Genetic testing can be performed on a blood sample or other tissue types and can confirm the presence of mutations in the ISPD gene.

Muscle Biopsy A muscle biopsy is another diagnostic tool used to diagnose LGMD2U. This involves taking a small sample of muscle tissue from the affected area, which is then examined under a microscope for signs of muscle damage [7]. Muscle biopsy can help confirm the presence of muscle atrophy and other characteristic features of LGMD2U.

Creatine Kinase (CK) Levels Elevated CK levels are often seen in patients with LGMD2U. CK testing can aid in diagnosis, especially in cases where the disease is suspected to be autosomal recessive [4]. However, it's essential to note that elevated CK levels can also be present in other conditions.

Other Diagnostic Tests In addition to genetic testing and muscle biopsy, other diagnostic tests may be used to assess the severity of LGMD2U. These include:

• 6-minute walking test
• North Star ambulatory assessment scale
• Time taken to climb four steps
• Time taken to rise from the floor
• Performance of upper limb [8]

These tests can help evaluate the functional impairment and muscle strength in patients with LGMD2U.

References

[4] Elevated CK levels are often seen in patients with LGMD2U, which can aid in diagnosis (Context #3).

[5] Genetic testing is the most accurate method for diagnosing LGMD2U by analyzing the DNA sequence of the ISPD gene (Context

Current Status of Drug Treatment for Autosomal Recessive Limb-Girdle Muscular Dystrophy Type 2U

Unfortunately, there is no specific treatment available for autosomal recessive limb-girdle muscular dystrophy (LGMD) type 2U. According to recent medical literature [2], no specific management protocol has been established for this condition, and management is based on the presentation of each individual case.

However, aggressive supportive care is essential in managing symptoms and improving quality of life for patients with LGMD type 2U [7]. This may include physical therapy, assistive devices, and medications to alleviate symptoms and manage complications.

Emerging Therapies

While there are no specific treatments available for LGMD type 2U, researchers are exploring various emerging therapies that may hold promise for the future. These include:

• Gene therapy: a potential treatment approach that involves replacing or repairing faulty genes [5].
• Exon skipping: a technique that allows for the production of a functional protein by "skipping" over the mutated exon [1].
• Stop codon read-through: a strategy that enables the cell to continue producing a functional protein despite the presence of a premature stop codon [5].

These emerging therapies are still in the early stages of research and require further investigation before they can be considered as potential treatments for LGMD type 2U.

Consultation with a Healthcare Professional

It is essential to consult with a healthcare professional for medical advice and treatment. They can provide personalized guidance on managing symptoms, improving quality of life, and exploring emerging therapies that may be relevant to your specific situation [4].

References:

[1] 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].

[2] Aug 15, 2019 — No specific treatment is available for any of the LGMD syndromes, though aggressive supportive care is essential.

[4] Please consult with a healthcare professional for medical advice and treatment. Print. Disease Overview. Any autosomal recessive limb-girdle muscular dystrophy ...

[5] These strategies include gene therapy, exon skipping, stop codon read through, and myostatin blocking. To learn more, read The Changing Landscape of LGMD ...

[7] Aug 15, 2019 — Although causative gene mutations have been well characterized for LGMD, no specific treatment is available for any of the LGMD syndromes yet.

Note: The numbers in square brackets refer to the corresponding search results provided in the context.

The differential diagnosis of autosomal recessive limb-girdle muscular dystrophy (LGMD) type 2U involves distinguishing it from other neuromuscular disorders. According to the literature, LGMD2U is a rare form of LGMD that can be challenging to diagnose due to its similarity in clinical features with other conditions.

Key diagnostic considerations:

• X-linked Becker muscular dystrophy (BMD): The similarity in clinical features between BMD and LGMD2U makes differential diagnosis difficult, especially in isolated male cases [15].
• Autosomal dominant limb-girdle muscular dystrophies: Other forms of LGMD, such as type 1, may also need to be ruled out through genetic testing and clinical evaluation.
• Other neuromuscular disorders: Conditions like myotonic dystrophy, facioscapulohumeral muscular dystrophy, and distal myopathies should also be considered in the differential diagnosis.

Diagnostic approaches:

• Clinical evaluation: A thorough medical history, physical examination, and assessment of muscle strength and function are essential for diagnosing LGMD2U.
• Genetic testing: Molecular genetic analysis can help identify mutations in the TRIM32 gene, which is associated with LGMD2U [10].
• Imaging studies: Muscle MRI may be used to support the diagnosis by showing characteristic features of LGMD2U.

References:

[10] 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.

[15] The similarity in clinical features of X-linked Becker muscular dystrophy (BMD) and the autosomal recessive limb-girdle (LGD) type of adult muscular dystrophy makes differential diagnosis of the isolated male case difficult. DNA probes complementary (cDNA) to the Duchenne/Becker muscular dystrophy g …