Adenosine monophosphate (AMP) deaminase deficiency is a condition that can affect the muscles used for movement (skeletal muscles). In many affected individuals, AMP deaminase deficiency does not cause any symptoms. People who do experience symptoms typically have fatigue, muscle pain (myalgia), or cramps after exercise or prolonged physical activity (exercise intolerance). Following strenuous activity, they often get tired more quickly and stay tired longer than would normally be expected. In rare cases, affected individuals have more severe symptoms including severe muscle weakness, low muscle tone (hypotonia), and muscle wasting (atrophy), but it is unclear whether these symptoms are due solely to AMP deaminase deficiency or additional health conditions. Exercise intolerance associated with AMP deaminase deficiency usually becomes apparent in childhood or early adulthood.

Myalgia

Painful sensation in the muscles.

Musculoskeletal Pain

Discomfort stemming from muscles, LIGAMENTS, tendons, and bones.

AMP deaminase deficiency is caused by mutations in the AMPD1 gene, which provides instructions for producing an enzyme called AMP deaminase. This enzyme is found in skeletal muscles, where it plays a role in producing energy. Skeletal muscle cells need energy to function and move the body.

Mutations in the AMPD1 gene often result in an AMP deaminase enzyme that cannot function and as a result, energy production in skeletal muscle cells is decreased. Skeletal muscles are particularly sensitive to decreases in energy during periods of exercise or increased activity when energy demands increase. The lack of AMP deaminase activity can result in fatigue, muscle weakness or pain, or other muscle problems in some people with AMP deaminase deficiency.

It is not known why some people with this condition do not experience symptoms. Researchers speculate that additional factors, both genetic and environmental, may determine whether a person develops the signs and symptoms of AMP deaminase deficiency.

Normal Function

The AMPD1 gene provides instructions for producing an enzyme called adenosine monophosphate (AMP) deaminase. This enzyme is found in the muscles used for movement (skeletal muscles), where it plays a role in producing energy. Specifically, during physical activity, this enzyme converts a molecule called adenosine monophosphate (AMP) to a molecule called inosine monophosphate (IMP) as part of a process called the purine nucleotide cycle. This cycle reuses molecules called purines, which are a group of building blocks of DNA (nucleotides), its chemical cousin RNA, and molecules such as AMP that serve as energy sources in the cell. As part of the purine nucleotide cycle, AMP deaminase converts AMP to IMP, and as the cycle continues, molecules are produced that the muscle cells can use for energy. Skeletal muscle cells need energy to function and move the body.

Health Conditions Related to Genetic Changes

Adenosine monophosphate deaminase deficiency

At least nine mutations in the AMPD1 gene have been found to cause AMP deaminase deficiency. This condition is characterized by skeletal muscle pain or weakness after exercise or prolonged physical activity (exercise intolerance). Most cases are caused by a mutation that results in a premature stop signal in the instructions for making AMP deaminase (written as Gly12Ter or Q12X). The resulting enzyme is abnormally short and nonfunctional and cannot participate in the purine nucleotide cycle. As a result, the process stalls and energy production in skeletal muscle cells is decreased. Skeletal muscles are particularly sensitive to decreases in energy during periods of exercise or increased activity when energy demands increase. The lack of AMP deaminase as a source of energy production can result in fatigue and muscle weakness or pain in some people with AMP deaminase deficiency.

It is not known why some people with this condition do not experience symptoms. Researchers speculate that additional factors, both genetic and environmental, may determine whether a person develops the signs and symptoms of AMP deaminase deficiency.

Other Names for This Gene

• Adenosine monophosphate deaminase-1 (muscle)
• AMP deaminase
• AMPD1_HUMAN
• MAD
• MADA

Genomic Location

AMP deaminase deficiency is one of the most common inherited muscle disorders in white populations, affecting 1 in 50 to 100 people. The prevalence is lower in African Americans, affecting an estimated 1 in 40,000 people, and the condition is even less common in the Japanese population.