Myoadenylate deaminase deficiency is one of the most common causes of metabolic myopathy. It affects 1 to 2% of the European population, although in most people it does not cause any symptoms.
Myoadenylate deaminase (AMPD1 gene)
Myoadenylate deaminase deficiency (MAD) is a form of myopathy of a metabolic nature characterized by myalgia or muscle pain after exertion and reduced exercise tolerance. Inherited cases are mainly caused by variants in the AMPD1 gene (the most frequent being C34T or c.34C>T), and follow an autosomal recessive mode of inheritance with incomplete penetrance. This means that not all people who have two copies of a variant in AMPD1 causing the deficiency become symptomatic.
The function of the enzyme myoadenylate deaminase is to convert adenosine monophosphate to inosine monophosphate and ammonia as part of purine nucleotide metabolism. This metabolic pathway is essential for energy production in skeletal muscle cells.
Since MAD usually causes mild symptoms in a small proportion of patients, it is questionable whether it has clinical relevance. However, recent studies suggest that it may have a deleterious impact on athletic performance. On the other hand, there are studies suggesting that MAD-related variants may even have a cardioprotective effect in patients with heart failure.
Genes analyzed
AMPD1
Bibliography
Del Coso J, Lucia A. Genetic Influence in Exercise Performance. Genes (Basel). 2021 Apr 27;12(5):651.
Urtizberea JA, Severa G, Malfatti E. Metabolic Myopathies in the Era of Next-Generation Sequencing. Genes (Basel). 2023 Apr 22;14(5):954.
Leońska-Duniec A, Maculewicz E, Humińska-Lisowska K, et al. AMPD1 C34T Polymorphism (rs17602729) Is Not Associated with Post-Exercise Changes of Body Weight, Body Composition, and Biochemical Parameters in Caucasian Females. Genes (Basel). 2020 May 16;11(5):558.
Lopez-Schenk R, Collins NL, Schenk NA, Beard DA. Integrated Functions of Cardiac Energetics, Mechanics, and Purine Nucleotide Metabolism. Compr Physiol. 2023 Dec 29;14(1):5345-5369.
Noury JB, Zagnoli F, Petit F, et al. Exercise efficiency impairment in metabolic myopathies. Sci Rep. 2020 May 29;10(1):8765.
Rannou F, Scotet V, Marcorelles P, Monnoyer R, Le Maréchal C. Effects of AMPD1 common mutation on the metabolic-chronotropic relationship: Insights from patients with myoadenylate deaminase deficiency. PLoS One. 2017 Nov 2;12(11):e0187266.
