Wednesday, 22 September 2010


Myoadenylate deaminase deficiency is a very common trait in the general population. Until now, this enzyme deficiency has been usually attributed to an erratic clinical entity characterized by rapid fatigue, myalgia and cramps after exercise, onset in late adolescence or early adulthood, equal distribution among males and females and, exept for the first period after onset, without features of progression to dystrophy or muscle tissue wasting. Some patients have also been reported to have experienced rhabdomyolysis and myoglobinuria (i.e. episodes of cell lysis followed by loss of muscle myoglobin in the urine). Nevertheless, the vast majority of patients appears to be asymptomatic, even if showing enzyme activity reduction at muscle biopsy and/or being carrier of what was considered to be the disease-mutation.

The myoadenylate deaminase enzyme is found in skeletal muscle, liver and red blood cells. The skeletal muscle isoform is called myoadenylate deaminase 1 and is encoded by the gene AMDP1. An AMDP1 “mutation” (C34T) was identified and demonstrated to prevent the synthesis of the enzyme. Indeed, C34T is estimated to be widespread, being homozygously represented in at least 1-3% of the general population. The estimated high frequency of homozygous individuals, who are mostly asymptomatic, has raised many doubts about the real pathogenicity of the C34T “mutation”(which should be more correctly referred to as a “polymorphism” rather than a mutaion) and other rarer mutation on the same gene. A recent study (2008) seems to indicate that the C34T variant (or other more rare mutations) is not differently distributed among healthy subjects and patients showing the characteristic picture of rapid fatigue, myalgia and cramps after exercise, whether or not these patients are also affected from neuromuscular diseases such as inherited, inflammatory, autoimmune or endocrine myopathies.

This study seems to indicate that a “primary” (i.e. genetically determined) myodenilate deaminase 1 deficiency is unlikely to be of clinical relevance and that the existence of a “secondary” myoadenylate deficiency  (i.e. caused by neuromuscolar diseases) may also be excluded.

The causes of the clinical ensemble characterized by rapid fatigue, myalgia and cramps after exercise are therefore still to be investigated, as well as an etiologic therapy remains unavailable. In theory, the administration of creatine monohydrate could provide an alternative source of energy for the anaerobic muscle tissue, whereas administration of D-ribose has proved to be ineffective in the long run. However, aerobic exercise can be encouraged, even if attention should be paid to cases presenting with myoglobinuria.


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