Brody myopathy

Alternate names

Brody disease; Sarcoplasmic reticulum -Ca2+ATPase deficiency

Definition

Brody myopathy is a condition that affects the skeletal muscles, which are the muscles used for movement.

Epidemiology

Brody myopathy is estimated to occur in 1 out of 10,000,000 people. Researchers suggest that this may be an underestimation as the diagnosis may go unrecognized.

Cause

• Mutations in the ATP2A1 gene cause Brody myopathy.
• The ATP2A1 gene provides instructions for making an enzyme called sarco(endo)plasmic reticulum calcium-ATPase 1 (SERCA1).
• The SERCA1 enzyme is found in skeletal muscle cells, specifically in the membrane of a structure called the sarcoplasmic reticulum.
• This structure plays a major role in muscle contraction and relaxation by storing and releasing positively charged calcium atoms (calcium ions).
• When calcium ions are transported out of the sarcoplasmic reticulum, muscles contract; when calcium ions are transported into the sarcoplasmic reticulum, muscles relax.
• The SERCA1 enzyme transports calcium ions from the cell into the sarcoplasmic reticulum, triggering muscle relaxation.

Gene mutations

• ATP2A1 gene mutations lead to the production of a SERCA1 enzyme with decreased or no function.
• As a result, calcium ions are slow to enter the sarcoplasmic reticulum and muscle relaxation is delayed.
• After exercise or strenuous activity, during which the muscles rapidly contract and relax, people with Brody myopathy develop muscle cramps because their muscles cannot fully relax.

Inheritance

Autosomal recessive inheritance, a 25% chance

• Brody myopathy is usually inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations.
• The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
• Some people with autosomal recessive Brody myopathy do not have an identified mutation in the ATP2A1 gene; the cause of the disease in these individuals is unknown.

Onset

Symptoms of Brody myopathy typically begin in childhood.

Signs and symptoms

• Affected individuals experience muscle cramping and stiffening after exercise or other strenuous activity, especially in cold temperatures.
• These symptoms typically begin in childhood.
• They are usually painless, but in some cases can cause mild discomfort.
• The muscles usually relax after a few minutes of rest. Most commonly affected are the muscles of the arms, legs, and face (particularly the eyelids).
• In some people with Brody myopathy, exercise leads to the breakdown of muscle tissue (rhabdomyolysis).
• The destruction of muscle tissue releases a protein called myoglobin, which is processed by the kidneys and released in the urine (myoglobinuria).
• Myoglobin causes the urine to be red or brown.

Diagnosis

Brody myopathy is suspected in people with the characteristic symptoms. The diagnosis may be confirmed using a combination of several different evaluations including:

• Physical examination
• Bloodwork to evaluate the level of certain proteins such as creatine kinase
• Muscle biopsy
• Electromyography

Treatment

• There is no one treatment for Brody myopathy.
• Certain muscle relaxants, such as dantrolene and blood pressure medications called calcium channel blockers, such as verapamil have been used with varying levels of success.

Prognosis

Symptoms of Brody myopathy may remain the same or slowly worsen with time. In advanced disease some people may experience some muscle loss (atrophy) and weakness.

NIH genetic and rare disease info

• NIH info on Brody myopathy

Brody myopathy is a rare disease.

Brody myopathy Resources
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