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.

• Pain

  Pain intensity at perception threshold for touch-evoked pain was, however, unaltered. Pinprick-evoked pain in the neuropathic areas was reduced from 53 +/- 11 to 29 +/- 10 mm (P < 0.05). [doi.org]

  A diagnosis of tension myalgia or myofascial-type pain is often considered when no objective findings are seen in the evaluation. [ncbi.nlm.nih.gov]

  Myoadenylate deaminase deficiency (MAD) constitutes the most common genetically determined enzymatic defect of the skeletal muscle (2% of the population), however, it causes clinical symptoms such us exercise-related muscle cramps and pain in quite a [neurologia.com]

• 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]

  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. [accessanesthesiology.mhmedical.com]

• Asymptomatic

  However, it may be possible that the homozygous asymptomatic subjects are not completely free of symptoms. Maybe these subjects are simply not very successful in sports. [slideheaven.com]

  Although a small percentage of mAMPD-deficient individuals present with exercise-induced cramping and pain, most are asymptomatic. [medlink.com]

  Although the molecular basis for this purine nucleotide catabolic derangement may typically be attributed to the inheritance of a single prevalent mutant allele, the clinical spectrum in the absence of other definable abnormalities can range from asymptomatic [ncbi.nlm.nih.gov]

  6}, pages={ 734-7 } } Manuel Castro-Gago, Carmen Gómez-Lado, +4 authors Miguel Angel Martín Published in Journal of child neurology 2011 DOI: 10.1177/0883073810390367 The spectrum of the adenosine monophosphate (AMP) deaminase deficiency ranges from asymptomatic [semanticscholar.org]

• Hyperthermia

  The present findings suggest that patients with myoadenylate deaminase deficiency (and the carrier state as well) may be at increased risk of malignant hyperthermia when subjected to anesthesia. [ncbi.nlm.nih.gov]

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

• Dyspnea

  Ventilatory muscle weakness - dyspnea. Nocturnal breathing problems, sleep apnea, excessive day time headache and sleepiness. Nocturnal hypercarbia, orthopnea, paradoxical breathing. [sites.google.com]

• Nausea

  Visual analog scales were used to record feelings of hunger, pleasantness and nausea. [doi.org]

  Although more studies are needed, D-ribose appears to be safe for most people: It may cause mild side effects, such as nausea, gastrointestinal discomfort, diarrhea, and headaches, particularly in extremely high doses (60 grams or more a day). [naturalhealthsherpa.com]

  GLYCOGENOLYSIS —McArdle’s disease: Caused by a myophosphorylase deficiency (see Mcardle’s disease) —Tarui’s disease: Caused by a phosphofructokinase deficiency, Tarui’s disease has features similar to those of McArdle’s disease, but there may also be nausea [rheumaknowledgy.com]

  Muscle fatigue which upon exercise can lead to severe cramps, nausea, vomiting, muscle damage and discoloration of urine. Disease varies widely in severity and progression. PHOSPHOGLYCERATE KINASE DEFICIENCY Age of onset: Childhood to adulthood. [mda.org.au]

  This form is indistinguishable from phosphofructokinase deficiency type VII or Tarui disease (PFKD) which is characterized by lifelong intolerance to vigorous exercise, often accompanied by cramps and nausea that are relieved by rest. [neuroweb.us]

• Vomiting

  GLYCOGENOLYSIS —McArdle’s disease: Caused by a myophosphorylase deficiency (see Mcardle’s disease) —Tarui’s disease: Caused by a phosphofructokinase deficiency, Tarui’s disease has features similar to those of McArdle’s disease, but there may also be nausea, vomiting [rheumaknowledgy.com]

  Muscle fatigue which upon exercise can lead to severe cramps, nausea, vomiting, muscle damage and discoloration of urine. Disease varies widely in severity and progression. PHOSPHOGLYCERATE KINASE DEFICIENCY Age of onset: Childhood to adulthood. [mda.org.au]

  The neonates sometimes lethal form usually presents in the first few days of life with poor feeding, vomiting and metabolic acidosis. [annalsofneurosciences.org]

  One subject vomited 10 min after consuming the meal containing fat and sodium propionate-enriched tomato sauce. On that occasion the test was stopped and the data set was excluded from the analysis. [doi.org]

  Fatty acid oxidation defects (FAODs): FAODs usually present with a history of hypoglycemia or coma after sustained exercise or prolonged fasting ( > 24 hours), intermittent bouts of weakness, lethargy, ataxia and coma or episodic vomiting. [neuroweb.us]

• Hypotension

  The study found that while adenosine-induced hypotension maintains cerebral blood flow, autoregulation is decreased at light hypotension and completely abolished at moderate hypotension. [web.archive.org]

• Myopathy

  Deficiency of the muscle-specific enzyme is apparently a common cause of exercise-induced myopathy and probably the most common cause of metabolic myopathy in the human. [mybiosource.com]

  However, the vast majority of homozygous subjects do not develop a metabolic myopathy. [slideheaven.com]

  Tarnopolsky, Metabolic Myopathies, CONTINUUM: Lifelong Learning in Neurology, 22, 6, (1829), (2016). [doi.org]

  Laboratory: Laboratory-based evidence for a metabolic myopathy should exist which may include but not be limited to elevated serum creatine kinase, an abnormal ischemic exercise test result, and/or an abnormal EMG. [rgbmgl.org]

• Myalgia

  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]

  A diagnosis of tension myalgia or myofascial-type pain is often considered when no objective findings are seen in the evaluation. [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]

• 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]

  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. [accessanesthesiology.mhmedical.com]

• 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]

• Urinary Retention

  Autonomic features palpitations, constipation, diarrhea, orthostatic intolerance, urinary retention, incontinence, ED, sweating abnormalities (hypo or hyperhidrosis), early satiety, blurred vision, dry eyes, dry mouth. [sites.google.com]

• Irritability

  Fasciculations 594 Case 97 A Man with Large and Stiff Muscles 601 Case 98 A Boy with Short Stature Small Jaw Muscle Hypertrophy and Stiffness 609 Case 99 An Elderly Woman with Muscle Spasms 612 Case 100 A Woman with Proximal Muscle Weakness and Neuromuscular Irritability [books.google.com]

  Overly acidic urine causes irritation that feels like a frequent urge to urinate (with little volume) and a "hot" urine. [en.wikipedia.org]

  Patients suffering with fibromyalgia suffer from constant pain, sleep disturbances, overwhelming fatigue, weakness, muscle stiffness and soreness, headaches, irritable bowel, anxiety and depression. [healthylifedoctors.com]

  Features that would suggest a steroid myopathy as opposed to relapse of myositis would be a normal CK, and absence of muscle membrane irritability on EMG. [sites.google.com]

• Lethargy

  Fatty acid oxidation defects (FAODs): FAODs usually present with a history of hypoglycemia or coma after sustained exercise or prolonged fasting ( > 24 hours), intermittent bouts of weakness, lethargy, ataxia and coma or episodic vomiting. [neuroweb.us]

  Another rare disorder linked to CPT II deficiency is manifest in infancy as hypoketotic hypoglycemia, hepatomegaly and hepatic failure, cardiomegaly and arrhythmias, lethargy, seizure, and coma. [emedicine.medscape.com]

  Symptoms occurs within first two years of life with Reye's-like episodes of lethargy, vomiting and coma precipitated by fasting state and associated with hypoketotic hypoglycemia. [annalsofneurosciences.org]

• Asthenia

  Approximately 10% of patients stop the drug because of adverse events, principally gastrointestinal intolerance and asthenia. CBC and liver function tests should be monitored every month. Riluzole does not produce an improvement in symptoms. [neuroweb.us]

  […] paresthesia, burning Negative: numbness or sensory ataxia ChLORIDE-PP Chronological evolution of symptoms Did the symptom occur in a focal nerve distribution before it became confluent (e.g., MMN vs length-dependent polyneuropathy) Distinguish weakness from asthenia [sites.google.com]

• 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].

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]

[…] in metabolic diseases; development of animal models of metabolic diseases, both to improve understanding of the diseases and to test possible treatments; development of enzyme replacement therapies; and development of gene therapies. [mda.org]

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]

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

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]

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]

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]

[…] 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]

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]

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]

Pathophysiology MADM is one of the three enzymes of the purine cycle. [accessanesthesiology.mhmedical.com]

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

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

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]

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]

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]

Here at VMK Naturopath north of Brisbane we are inspired and committed to creating and integrating effective and consistent preventative and treatment strategies that deliver health- promoting solutions to all ages. [vmknaturopath.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.