Adenosine monophosphate deaminase 1 deficiency

In many people, adenosine monophosphate deaminase 1 (AMPD1) deficiency does not cause any symptoms. The reasons for this are unclear. People who do have symptoms typically have muscle pain (myalgia) or weakness after exercise or prolonged physical activity. They often get tired more quickly and stay tired longer than others. Some people have more severe symptoms, but it is unclear whether these symptoms are due solely to AMPD1 deficiency, or additional factors.^[1]

Adenosine monophosphate deaminase 1 (AMPD1) deficiency is caused by changes (mutations) in the AMPD1 gene. This gene gives the body instructions to make an enzyme called AMP deaminase, which plays a role in producing energy in skeletal muscle cells. Mutations in the AMPD1 gene disrupt the function of AMP deaminase, which impairs the ability of muscle cells to make energy. This lack of energy can lead to the muscle problems associated with AMPD1 deficiency.^[1]

Other types of AMPD deficiency are known as the acquired type (due to a different muscle or joint condition), and the coincidental inherited type (due to both mutations in the AMPD1 gene and a separate muscle or joint disorder).^[1]

This condition is inherited in an autosomal recessive manner, which means that both copies of the responsible gene in each cell must have changes (mutations) for a person to be affected. The parents of a person with an autosomal recessive condition each carry one copy of the mutated gene and are referred to as carriers. Carriers are not affected and typically do not have signs and symptoms of the condition. When two carriers of an autosomal recessive condition have children, each child has a 25% (1 in 4) chance to be affected, a 50% (1 in 2) chance to be a carrier like each parent, and a 25% chance to be unaffected and not be a carrier.

There are many people who have mutations in both copies of the gene responsible for AMPD1 deficiency, but do not have any signs or symptoms (are unaffected).  The reasons for this are unclear.^[1]

Although there is no cure for AMP1 deficiency, there may be ways to manage symptoms. One possibility is the use of a sugar called D-ribose.^[2][3][4] This sugar is easily absorbed in digestive system and rapidly cleared by metabolic pathways. It may provide an additional source of energy for muscle' however, the helpful effects of D-ribose are short-term.^[3][4]

People with this condition may first develop symptoms during childhood, adolescence, or as young or older adults. Many people do not have any symptoms. Those with symptoms typically have only rapid fatigue, cramps or muscle pain (myalgia) after exercising.^[5]  In some cases, symptoms may progress over the first few years, but then the condition usually stabilizes (does not get worse).^[5] In many people, it is not progressive at all.^[6] There are no known consistent complications of the condition.^[6] There is no evidence of muscular dystrophy or muscular wasting in affected people, and it does not affect smooth muscle or other organs (only skeletal muscle). Life expectancy is not shortened.^[5]