Myoadenylate Deaminase Deficiency

Inherited or secondarily acquired disorder of muscle purine nucleotide metabolism. The clinical manifestations include exercise-induced myopathy, postexertional muscle weakness or cramping, prolonged fatigue after exertion, and limping infant caused by benign congenital hypotonia. Generalized muscle pair is often manifested.

Muscle Adenosine Monophosphate Deaminase Deficiency; MADA Deficiency; AMP Deaminase.

This defect is specific to skeletal muscle and may be one of the commonest genetic defects. The heterozygosity is believed to be 1 in 5. It is found in 2% of muscle biopsies of patient presenting with muscle weakness or poor exercise tolerance. It has equal sex distribution.

The primary deficiency is transmitted as autosomal dominant. The AMPD1 gene encoding for muscle adenosine monophosphate deaminase (MADM) is located on chromosome 1. The mutant allele is frequent in white people. In secondary cases, the defect could be caused by a limitation in AMPD1 transcript availability. In those cases, the participation of the MADM deficit to the patient's phenotype is unclear.

MADM is one of the three enzymes of the purine cycle. In the muscle, this cycle removes adenosine monophosphate (AMP) formed during exercise to favor formation of ATP from adenosine diphosphate (ADP), releases ammonia (NH3) and inosine monophosphate, stimulators of glycolysis and thus energy production, and produces fumarate, an intermediate of the citric acid cycle. This impaired muscular energy production during exercise seems to be the cause of the muscular dysfunction.

Absence of elevation of plasma ammonia following exercise (as in normal subjects); activity of MADM is lower than 2% in inherited cases and between 2% and 15% in secondary cases. Onset is in childhood or adolescence in nearly 50% of cases.

In case of primary defect, postexercise symptoms are the main manifestations: early fatigue, cramps, or myalgias sometimes accompanied by myoglobinuria and increased creatine kinase following moderate to vigorous exercise. Administration of oral ribose could improve muscle strength and endurance.

In primary defects, check muscle strength and creatine kinase level; exclude any associated cardiomyopathy by echocardiography. In secondary defects, follow the same precautions as for the associated disease (myopathy, collagen vascular disease, periodic paralysis).

Muscle energy depends on glucose availability—prevent hypoglycemia and prolonged use of a tourniquet leading to ischemia. As in many other muscular disorders, it is safer to avoid succinylcholine.

Do not use succinylcholine to avoid rhabdomyolysis, hyperkalemia, and cardiac arrhythmias.