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
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
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
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
Do not use succinylcholine to avoid
rhabdomyolysis, hyperkalemia, and cardiac arrhythmias.
Van den Bergh G, Vincent M-F, Marie S: Disorders of purine and pyrimidine
metabolism, in Fernandes J, Saudubray J-M, Van den Bergh G (eds): Inborn Metabolic Diseases. 3rd ed.
Berlin, Springer, 2000, p 355.