The clinical presentation of myoadenylate deaminase deficiency stems from the absence of the enzyme that facilitates the conversion of adenosine monophosphate (AMP) to inosine monophosphate (IMP) and ammonia (NH3) as a byproduct [1] [2]. As this process plays an important role in the generation of energy, the vast majority of patients reports symptoms that are related to exercise and physical activity [1] [3] [4]. Skeletal muscle pain (myalgia, which is sometimes be accompanied by cramping), frequent reports of fatigue, and weakness are the principal complaints [1] [3] [4] [5] [6]. Virtually any skeletal muscle can be affected - the facial muscles, the upper and lower extremities, or even a generalized presentation may be seen, and atrophy might also be reported [4] [6]. The duration of symptoms is quite long before the diagnosis is made, as up to 10 years may pass before clinical suspicion is raised [1] [3] [4] [5] [6]. An atypical presentation of constant muscle pain without an exertional association has been noted in rare cases [6]. The prevalence of myoadenylate deaminase deficiency is high: between 1-2% of the population is established to suffer from mutations that produce this effect. The deficiency shows an autosomal recessive pattern of inheritance with a very broad phenotypic range [2]. Furthermore, other neuromuscular diseases may be concomitantly present [2] [3], which is why the diagnosis of myoadenylate deaminase deficiency may not be easy to make.

• Fatigue

  The individuals with MDD fatigued after performing only 28% as much work as their non-MDD counterparts. Muscle biopsies were obtained from the four MDD patients and the eight non-MDD patients at rest and following exercise to the point of fatigue. [doi.org]

  Skeletal muscle pain (myalgia, which is sometimes be accompanied by cramping), frequent reports of fatigue, and weakness are the principal complaints. [symptoma.com]

  leading to central fatigue [ 2 ]. [omicsonline.org]

• Delayed Speech Development

  In "secondary" MADA deficiency, the clinical findings have been variable with delayed motor development, hypotonia, cardiomyopathy, delayed speech development, and generalized weakness. [ncbi.nlm.nih.gov]

• Myalgia

  Although most deficient subjects are asymptomatic, some suffer from exercise-induced myalgia suggesting a causal relationship between a lack of enzyme activity and muscle function. [ncbi.nlm.nih.gov]

  CONCLUSION: MAD deficiency must be ruled out in every patient with exertional myalgia and increased CK which normalizes when asymptomatic. [pesquisa.bvsalud.org]

  A 7 year old boy is referred with intense myalgias after physical exertion associating increased creatinkinase level 3,273 UI/L (normal 24-195) which goes down in rest period to increase again with myalgias during exercise. [neurologia.com]

  Skeletal muscle pain (myalgia, which is sometimes be accompanied by cramping), frequent reports of fatigue, and weakness are the principal complaints. [symptoma.com]

• Muscle Weakness

  This report concerns two unrelated males; one had sarcoidosis, sarcoid myopathy and muscle weakness, and the other had exercise-induced weakness and myalgia. [ncbi.nlm.nih.gov]

  […] with Weakness Elevated Cholesterol and Serum Creatine Kinase Levels 550 Case 88 An Older Woman with Leg Weakness and Atrophic Muscle Fibers on Biopsy 554 Case 89A A Woman with Muscle Weakness and a Skin Rash 559 Case 90 A Man with Muscle Pains 567 Case [books.google.com]

  In rare cases, affected individuals have more severe symptoms including severe muscle weakness, low muscle tone (hypotonia), and muscle wasting (atrophy), but it is unclear whether these symptoms are due solely to AMP deaminase deficiency or additional [ghr.nlm.nih.gov]

• Muscle Cramp

  Although rarely diagnosed in children, MAD deficiency must be included in the differential diagnosis of syndromes with exercise intolerance Keywords Children Ischemic forearm exercise test Metabolic disorders Muscle cramps Muscle disorders Muscle pain [neurologia.com]

  In contrast, 35 unrelated patients presenting with exercise-related muscle cramps or pains showed normal histochemical MAD activity. [ncbi.nlm.nih.gov]

• Exercise-induced Muscle Pain

  A 55 years old patient suffering from exercise-induced muscle pain and stiffness due to primary myoadenylate deaminase deficiency has been successfully treated with D-ribose since 1984: single doses of 4 grams administered at the beginning of exercise [ncbi.nlm.nih.gov]

  muscle pain, occasionally rhabdomyolysis, and idiopathic hyperCKemia. [semanticscholar.org]

  Observations on two brothers with exercise-induced muscle pain. J Neurol Sci. 1982 Jan; 53(1):125-36. Conal C. Kar, PhD, Carl M. Pearson, MD. Muscle Adenylate Deaminase Deficiency. Report of six new cases. Arch Neurol. 1981 May; 38(5):279-81. [revistas.proeditio.com]

  Showing of 9 | Medical Terms Other Names Learn More: HPO ID 80%-99% of people have these symptoms Exercise-induced muscle fatigue 0009020 Exercise-induced myalgia Exercise-induced muscle pain Muscle pain on exercise Muscle pain with exercise Muscle pain [rarediseases.info.nih.gov]

  Hübner Summary A 55 years old patient suffering from exercise-induced muscle pain and stiffness due to primary myoadenylate deaminase deficiency has been successfully treated with D-ribose since 1984: single doses of 4 grams administered at the beginning [doi.org]

• Muscular Atrophy

  The diagnoses in the 13 patients were: polyneuropathy (n = 5), infantile spinal muscular atrophy (n = 3), congenital myopathy with type 2 fibre atrophy, facioscapulohumeral myopathy, polymyositis, myotonic dystrophy and hyperornithinaemia with gyrate [ncbi.nlm.nih.gov]

  He is currently involved in multiple clinical trials of novel genetic interventions for the treatment of spinal muscular atrophy and Duchenne muscular dystrophy. [books.google.com]

  Spinal muscular atrophies: Amyotrophic lateral sclerosis (ALS), or motor neuron disease Infantile progressive spinal muscular atrophy Intermediate spinal muscular atrophy Juvenile spinal muscular atrophy Adult spinal muscular atrophy Inflammatory myopathies [hopkinsmedicine.org]

  ADULT SPINAL MUSCULAR ATROPHY Age of onset: 18 to 50 years. Weakness in the tongue, hands or feet which slowly spreads to other parts of the body. A relatively mild form of spinal muscular atrophy, it has little impact on life expectancy. [mda.org.au]

• Withdrawn

  Blood was withdrawn 2, 5 10, and 15 min after exercise. For lactate and pyruvate measurement, 1 mL blood was withdrawn in a tube containing 2 mL perchloric acid 1M previously cooled to 0°C. [journals.plos.org]

• Areflexia

  67 An Elderly Woman with a Progressive Neuropathy 429 Case 68 A Young Woman with Difficulty Swallowing 433 Case 69 A Young Woman with Intermittent Weakness and a Positive Family History of Similar Problems 436 Case 70 A Woman with Muscle Weakness and Areflexia [books.google.com]

The diagnostic workup of myoadenylate deaminase deficiency should start with a thorough patient history that will reveal the symptoms and their duration, as well as onset and progression. Clinical suspicion can be raised when an association is made between exercise and the appearance of complaints, in which case a more detailed approach should be sought. Elevation of creatine kinase (CK) is nonspecific, but very frequently found in this patient population [3] [5]. One of the key laboratory tests that point to a deficiency of myoadenylate deaminase is the evaluation of lactate, pyruvate, and ammonia levels 10 minutes after resting from physical activity [1] [2] [5]. In this condition, the normal rise in lactate is typically not followed by elevations of ammonia [2]. To further solidify the diagnosis, a muscle biopsy that uses specific stains to determine enzymatic activity is recommended by some authors [2] [3] [4] [6]. As a definitive method, genetic studies that detect mutations in the MAD gene located on chromosome 1 may be employed [2] [3] [7].

L-Carnitine treatment led to gradual improvement in exercise tolerance and cognitive performance; plasma and tissue carnitine levels returned to normal, and echocardiographic evidence of left ventricular hypertrophy disappeared. [ncbi.nlm.nih.gov]

As in the first edition, treatment is discussed extensively. Details are given for dietary treatment and drug administrations in acute situations, during infections and in maintenance treatment. [books.google.com]

The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment. [orpha.net]

Treatment of adenosine deaminase deficiency is by bone marrow or stem cell transplantation and enzyme replacement therapy. Somatic cell gene therapy is being evaluated as well. [merckmanuals.com]

Other muscle enzymes are also depleted, although not as severely, and the prognosis in such cases is dictated by the primary disease. [ncbi.nlm.nih.gov]

Prognosis - Adenosine monophosphate deaminase deficiency Not supplied. Treatment - Adenosine monophosphate deaminase deficiency Not supplied. Resources - Adenosine monophosphate deaminase deficiency [checkorphan.org]

It may provide an additional source of energy for muscle' however, the helpful effects of D-ribose are short-term.[3][4] Last updated: 9/6/2016 Prognosis Prognosis People with this condition may first develop symptoms during childhood, adolescence, or [rarediseases.info.nih.gov]

To date, genetic determinants of prognosis and survival in patients with heart failure have not been established. [j-circ.or.jp]

Deficiency of myoadenylate deaminase is heterogeneous in etiology and results in derangement of purine nucleotide catabolism and interconversion. [ommbid.mhmedical.com]

Etiology The vast majority of patients with this disease are homozygous for the nonsense C34-T mutation in the AMPD1 (adenosine monophosphate deaminase 1) gene. [orpha.net]

Sixty indoor patients, admitted to our hospital, having pleural effusions and suffering from varying etiologies were included in this study. [ncbi.nlm.nih.gov]

Molecular epidemiology seeks to determine whether a biologically-plausible candidate gene with an association to a well-defined disease affects 1) etiology, 2) risk stratification, 3) prognosis, and 4) design of novel therapeutic interventions. [j-circ.or.jp]

Summary Epidemiology About 1-2% of the Caucasian population carries the genetic defect causing myoadenylate deaminase deficiency, but only a minority of carriers develop symptoms. [orpha.net]

[…] joint symposium held in Gmunden, Austria in June 1997 (and dedicated to the memory of Andre deVries), these 164 papers are relevant to research interests in molecular biology, biochemical pharmacology, biochemistry, developmental biology, immunology, epidemiology [books.google.com]

PAGE TOP Molecular epidemiology in heart failure A molecular epidemiology approach was used to determine predictors of survival in patients with heart failure. [j-circ.or.jp]

These investigators provided an overview of the current knowledge about epidemiology, clinical features, and pathophysiology of IMNM, as well as treatment strategies. [aetna.com]

It appears that the general spectrum of myopathies described in the world literature is also seen in India, although the prevalence is difficult to ascertain, as there is very little published epidemiological data. [annalsofneurosciences.org]

For more detailed information, particularly with respect to pathophysiology and genetics, we highly recommend the seventh edition of The Metabolic Basis of Inherited Disease, by Charles R. Scriver et al. (McGraw-Hill, 1995). [books.google.com]

References Ording H: Pathophysiology of malignant hyperthermia. [anesthesiology.pubs.asahq.org]

The genetic background of a person likely plays a role in determining the response to the complex pathophysiology of heart failure. To date, genetic determinants of prognosis and survival in patients with heart failure have not been established. [j-circ.or.jp]

However, the understanding of pathophysiological mechanisms and treatment strategies still requires further investigation. [aetna.com]

The pathophysiological principles of metabolic myopathies may be simplified into a logical biochemical cascade. [emedicine.medscape.com]

55 years old patient suffering from exercise-induced muscle pain and stiffness due to primary myoadenylate deaminase deficiency has been successfully treated with D-ribose since 1984: single doses of 4 grams administered at the beginning of exercise prevented [ncbi.nlm.nih.gov]

Prevention - Adenosine monophosphate deaminase deficiency Not supplied. Diagnosis - Adenosine monophosphate deaminase deficiency Not supplied. Prognosis - Adenosine monophosphate deaminase deficiency Not supplied. [checkorphan.org]

This mutation creates an early stop codon thus preventing the synthesis of an enzymatically active protein. The deficiency disrupts the purine nucleotide cycle, and thus muscle energy production. [orpha.net]

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. [accessanesthesiology.mhmedical.com]

Currently, Adenosine Monophosphate Deaminase 1 Deficiency Disorder may not be preventable, since it is a genetic disorder. [dovemed.com]

1. Rannou F, Uguen A, Scotet V, et al. Diagnostic Algorithm for Glycogenoses and Myoadenylate Deaminase Deficiency Based on Exercise Testing Parameters: A Prospective Study. PLoS One. 2015;10(7):e0132972.
2. Tarnopolsky MA, Parise G, Gibala MJ, Graham TE, Rush JWE. Myoadenylate deaminase deficiency does not affect muscle anaplerosis during exhaustive exercise in humans. J Physiol. 2001;533(Pt 3):881-889.
3. Teijeira S, San Millán B, Fernández JM, et al. Myoadenylate deaminase deficiency: clinico-pathological and molecular study of a series of 27 Spanish cases. Clin Neuropathol. 2009;28(2):136-142.
4. Abe M, Higuchi I, Morisaki H, Morisaki T, Osame M. Myoadenylate deaminase deficiency with progressive muscle weakness and atrophy caused by new missense mutations in AMPD1 gene: case report in a Japanese patient. Neuromuscul Disord. 2000;10(7):472-477.
5. Lim L, Palayer M, Bruneau A, et al. Myoadenylate deaminase deficiency: a frequent cause of muscle pain A case detected by exercise testing. Ann Biol Clin (Paris). 2017;75(4):445-449.
6. Ahmed A, Lowden MR. Chronic Non-Exertional Myalgia and Myoadenylate Deaminase Deficiency: a Possible Association. J Clin Med Res. 2009;1(1):56-57.
7. Morisaki T, Gross M, Morisaki H, Pongratz D, Zöllner N, Holmes EW. Molecular basis of AMP deaminase deficiency in skeletal muscle. Proc Natl Acad Sci U S A. 1992;89(14):6457-6461.