X-linked myopathy with excessive autophagy

X-linked Myopathy with Excessive Autophagy (XMEA): A Rare Genetic Condition

X-linked myopathy with excessive autophagy (XMEA) is a rare genetic condition characterized by childhood or adult-onset of slowly progressive muscle weakness [1]. It is an X-linked recessive skeletal muscle disorder, meaning it primarily affects males due to the location of the mutated gene on the X chromosome [3][5].

The condition is marked by unique histopathological findings and excessive autophagy, which is the process of breaking down damaged or unnecessary cell parts [2]. Autophagy failure leads to progressive vacuolation and atrophy of skeletal muscles, resulting in muscle weakness [6][9].

XMEA is a rare disorder characterized by slow progressive muscle weakness and distinctive pathology of excessive autophagic vacuoles on muscle biopsy [8]. The condition is linked to the VMA21 gene, which plays a crucial role in autophagy regulation [7][10].

Key Features:

• Childhood or adult-onset of slowly progressive muscle weakness
• Unique histopathological findings and excessive autophagy
• X-linked recessive skeletal muscle disorder primarily affecting males
• Autophagy failure leading to progressive vacuolation and atrophy of skeletal muscles

References: [1] - Context 1: Nov 22, 2021 — X-linked myopathy with excessive autophagy (XMEA) is a very rare genetic condition. [2] - Context 2: A rare X-linked myopathy characterized by childhood or adult-onset of slowly progressive muscle weakness and unique histopathological findings. [3] - Context 3: X-linked myopathy with excessive autophagy (XMEA) is an X-linked recessive skeletal muscle disorder characterized by childhood onset of progressive muscle ... [5] - Context 5: X-linked myopathy with excessive autophagy (XMEA) is an X-linked recessive skeletal muscle disorder characterized by childhood onset of progressive muscle ... [6] - Context 6: Apr 2, 2024 — X-linked myopathy with excessive autophagy (XMEA) is a little-known disease linked to the VMA21 gene. It leads to autophagy failure with ... [7] - Context 7: by M Rajeshwari · 2022 · Cited by

Common symptoms of X-linked myopathy with excessive autophagy (XMEA) include:

• Muscle weakness, especially in the legs [1]
• Diminished muscle tone (hypotonia or "floppiness") [7]
• Feeding difficulties [7]
• Severe progressive muscle weakness [4][6]
• Proximal muscles of the lower extremities are primarily affected [5]

Other symptoms may include:

• Abnormality of metabolism/homeostasis, with elevated circulating creatine kinase concentration [2]
• Abnormality of the cardiovascular system [2]
• Muscle wasting and loss of ambulation, leading to wheelchair-bound status in many patients [3]

It's worth noting that XMEA is a rare disorder, and symptoms can vary from patient to patient.

References:

[1] Nov 22, 2021 — The most common feature of XMEA is muscle disease (myopathy) and slowly worsening muscle weakness, especially in the legs. [2] Clinical features · Abnormality of metabolism/homeostasis. Elevated circulating creatine kinase concentration · Abnormality of the cardiovascular system. [3] While onset is usually in childhood, it can range from infancy to adulthood. Many patients lose ambulation and become wheelchair-bound. Other organ systems... [4] by T Alon · 2021 · Cited by 6 — XMEA is a rare disorder characterized by slow progressive muscle weakness and distinctive pathology of excessive autophagic vacuoles on muscle biopsy. [5] by I Munteanu · 2015 · Cited by 23 — X-linked myopathy with excessive autophagy (XMEA) is characterized by weakness and wasting primarily of the proximal muscles of the lower extremities. [6] by T Alon · 2021 · Cited by 6 — XMEA is a rare disorder characterized by slow progressive muscle weakness and distinctive pathology of excessive autophagic vacuoles on muscle biopsy. [7] Common symptoms include mild to profound muscle weakness, diminished muscle tone (hypotonia or “floppiness”), feeding difficulties, and potentially severe...

Diagnostic Testing for X-linked Myopathy with Excessive Autophagy (XMEA)

According to the available information, diagnostic testing for XMEA can be made by two methods:

• Muscle Biopsy: A muscle biopsy can diagnose XMEA and findings are consistent across all patients with XMEA [1].
• Genetic Testing: Genetic testing of the VMA21 gene is recommended to confirm a diagnosis of XMEA [7].

Additionally, electrodiagnostic (EDx) testing may also be used to support a diagnosis of XMEA. EDx testing usually shows widespread complex repetitive and myotonic discharges, even in muscles unaffected clinically [3][4]. However, it's essential to note that there is no effective treatment for XMEA, and the differential diagnoses include other hereditary myopathies with autophagic vacuoles such as [8].

It's also worth noting that diagnostic testing for XMEA should be performed by a qualified healthcare professional or a genetic counselor.

References:

[1] - Muscle biopsy can diagnose XMEA and findings are consistent across all patients with XMEA. [3][4] - Electrodiagnostic (EDx) testing usually shows widespread complex repetitive and myotonic discharges, even in muscles unaffected clinically. [7] - The VMA21 gene is associated with X-linked myopathy with excessive autophagy ... Diagnostic testing of this gene is recommended to ... [8] - There is no effective treatment for XMEA. The differential diagnoses include other hereditary myopathies with autophagic vacuoles such as...

Treatment Options for X-linked Myopathy with Excessive Autophagy (XMEA)

According to the available information, there are some treatment options being explored or used in managing XMEA.

• Tamoxifen: Studies have shown that tamoxifen can effectively delete VMA21 from skeletal muscle, which is a key factor in the development of XMEA [6]. Treatment with tamoxifen for 5 days or chronic tamoxifen treatment has been found to be effective in reducing autophagic dysfunction.
• Rapamycin: Another study used rapamycin, an MTOR inhibitor, to augment colchicine's myotoxic effect by increasing the autophagic flux. This resulted in an acute myopathy with muscle damage [7].
• Other medications: In addition to these specific treatments, other medications such as β-blockers or diuretics, ACE inhibitors, Ca blockers, and anticoagulants are generally used in drug therapies for XMEA patients [8].

It's essential to note that the effectiveness of these treatment options may vary depending on individual cases, and more research is needed to fully understand their impact on XMEA.

References: [6] Inoue M (2023) - Treatment with tamoxifen for 5 days or chronic tamoxifen treatment effectively deleted VMA21 from skeletal muscle. [7] Ching JK (2013) - Using the MTOR inhibitor rapamycin we augmented colchicine's myotoxic effect by increasing the autophagic flux; this resulted in an acute myopathy with muscle damage. [8] Sugie K (2022) - In addition, β-blockers or diuretics, ACE inhibitors, Ca blockers, and anticoagulants are generally used in drug therapies.

The differential diagnosis for X-linked myopathy with excessive autophagy (XMEA) includes several other hereditary myopathies that present with similar histopathological findings, such as:

• Acid maltase deficiency
• Danon disease
• Other hereditary myopathies with autophagic vacuoles, including rimmed vacuolar myopathy [4][6]

These conditions can be distinguished from XMEA based on their specific genetic and pathological features. For example, acid maltase deficiency is caused by mutations in the GAA gene, while Danon disease is caused by mutations in the LAMP2 gene [4].

It's worth noting that there is no effective treatment for XMEA, and a definitive diagnosis can only be made through genetic testing or histopathological examination of muscle tissue [6][9].