Myoadenylate deaminase deficiency

Sabina, R. L. Myoadenylate deaminase deficiency. A common inherited defect with heterogeneous clinical presentation. Neurol. Clin. 18 185-194,2000. 

Myoadenylate deaminase deficiency is a recessive disorder that affects approximately 1 -2% of populations of European descent, but appears considerably rarer in Asian populations. Myoadenylate deaminase, also called adenosine monophosphate (AMP) deaminase, is an enzyme that converts AMP to inosine monophosphate (IMP). Its deficiency results in excess AMP, which is lost by excretion with disturbances in energy generation. Symptoms of severe fatigue and muscle pain can result. 

In muscle, a unique nucleotide reutilization pathway, known as the purine nucleotide cycle, uses three enzymes myoadenylate deaminase, adenylosuccinate synthetase, and adenylosuccinate lyase. In this cycle, AMP is converted to IMP with formation of NH3, and IMP is then reconverted to AMP. Myoadenylate deaminase deficiency produces a relatively benign disorder of muscle... 

Chapter 21), which is characterized by muscle fatigue following exercise (see Myoadenylate Deaminase Deficiency). 

In view of these 18 cases, it seems clear that pristine myoadenylate deaminase deficiency is usually s3nnptomatic, and that the view that symptoms ought not be attributed to the deficiencylO is sorely misguided. The same conclusion was reached by Keleman, et al, who found a 1.5% incidence in the muscle biopsy population, but a 5-6 fold higher incidence in cases coded as exertional myalgias. 

The best available evidence indicates that myoadenylate deaminase deficiency is genetically determined via autosomal recessive inheritance (1) Two affected sibling pairs have now been reported >. (2) Patients with the muscle deficit have normal... 

The prognosis in myoadenylate deaminase deficiency appears to be excellent, with no evidence for progressive debilitation or structural damage in the absence of other disease, and therapy should be aimed at reassurance, and the avoidance of hazardous and ineffective long-term drug treatment. 

Hoffman, R.S. Schoenfeldt, and N. Singh. 1980. Myoadenylate deaminase deficiency. Muscle biopsy and muscle culture in a patient with gout. J. Neurol. Sci. 47 191-202. 

Sabina, R.L., J. L. Swain, B. M. Patten, T. Ashlzawa, W.E. O Brien, and E.W. Holmes. 1980. Disruption of the purine nucleotide cycle. A potential explanation for muscle dysfunction in myoadenylate deaminase deficiency. J. Clin. Invest. 66 1419-1423. 

Mercelis, R., J.J. Martin, I. Dehaene, Th. deBarsy, and G. Van den Berghe. 1981. Myoadenylate deaminase deficiency in a patient with facial and limb girdle myopathy. J. Neurol. 225 157-166. 

Hayes, D.J., B.A. Summers, and J.A. Morgan-Hughes. 1982. Myoadenylate deaminase deficiency or not Observations on two brothers with exercise-induced muscle pain. J. Neurol. Sci. 

Fishbein, W.N., J. I. Davis, K. Nagarajan, J.W. Winkert, and J.W. Foellmer. 1980. Immunologic distinction of human muscle adenylate deaminase from the isozyme(s) in human peripheral blood cells implications for myoadenylate deaminase deficiency. Arch. Biochem. Biophys. 205 360-364. 

Myoadenylate deaminase deficiency verification on repeat biopsy, fresh or frozen, and origin of the residual enzyme. IRCS Med. Sci. 9 103-104. 

Fishbein, W.N., V.W. Armbrustmacher, and J.L. Griffin. 1980. Skeletal muscle adenylate deaminase, adenylate kinase, and creatine kinase in myoadenylate deaminase deficiency and malignant hyperthermia. Clin. Res. 28 288A. 

The broad spectrum of clinical presentation highlights the importance of particular steps in purine and pyrimidine metabolism to different cells and tissues and should have assisted in the development of appropriate treatment. Unfortunately, only three of the nineteen disorders described can be treated successfully hereditary orotic aciduria with life-long uridine, 2,8-di-hydroxyadenine lithiasis with allopurinol. ADA deficiency is treatable by bone marrow transplantation (BHT), or enzyme replacement with polyethylene glycol (PEG)-ADA, but the cost is prohibitive. Er/throcyte-encapsu-lated ADA is effective and less expensive. Oral ribose is reportedly beneficial in myoadenylate deaminase deficiency [1, 4] and also in adenylosucci-nase deficiency [1, 5]. PNP deficiency is also treatable by BMI. 

Zollner N, Reiter S, Pongratz D, Reimers CD, Gerbitz K, Paetzke I, Deufel T, Hubner G. Myoadenylate deaminase deficiency successful symptomatic therapy by high dose oral administration of ribose. Klin Wochenschr 1986 64 1281-1290... 

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