Adenosine Monophosphate Deaminase Deficiency type 1

Adenosine Monophosphate Deaminase Deficiency type 1
Classification and external resources

Adenosine monophosphate
OMIM 102770

Adenosine monophosphate deaminase deficiency type 1 is also called myoadenylate deaminase deficiency. It a recessive genetic metabolic disorder that affects approximately 1–2% of populations of European descent.[1] It appears to be considerably rarer in Asian populations.[1] The genetic defect causing this is AMP deaminase[1] though there is also an acquired form of AMP deficiency.

Contents

Causes

AMP deaminase is an enzyme that converts adenosine monophosphate (AMP) to inosine monophosphate (IMP), freeing an ammonia molecule in the process. It is a part of the metabolic process that converts sugar, fat, and protein into cellular energy. In order to use energy, a cell converts one of the above fuels into adenosine triphosphate (ATP) via the mitochondria. Cellular processes, especially muscles, then convert the ATP into adenosine diphosphate (ADP), freeing the energy to do work.

During heavy or prolonged mild to moderate activity, other enzymes convert two molecules of ADP into one ATP molecule and one AMP molecule, making more ATP available to supply energy. AMP is normally converted into IMP by myoadenylate deaminase — so myoadenylate deaminase deficiency reduces energy that would be available to the cell through the Purine nucleotide cycle. Normally, excess AMP builds up in the cell and is eventually metabolized in the liver. In persons with a defective enzyme, 5'-nucleotidase removes the ribose and phosphorus from AMP, increasing levels of cellular and circulating adenosine by 16x - 25x.[2][3]

Effects of failure to deaminate the AMP molecules

This failure to deaminate the AMP molecules has three major effects. First, significant amounts of AMP are lost from the cell and the body. Second, ammonia is not freed when the cell does work. Third, the level of IMP in the cell is not maintained.

Symptoms

The majority of people with the AMPD gene are asymptomatic, but others have symptoms including early fatigue, muscle pain and muscle cramping.[5]

Fatigue
Muscle pain
Muscle cramping
Muscle weakness

Treatment

It is important for MADD patients to maintain strength and fitness without exercising or working to exhaustion. Learning this balance may be more difficult than normally, as muscle pain and fatigue may be perceived differently than normal individuals.[12]

Symptomatic relief from the effects of MADD may sometimes be achieved by administering ribose orally at a dose of approximately 10 grams per 100 pounds (0.2 g/kg) of body weight per day. and exercise modulation as appropriate. Taken hourly, ribose provides a direct but limited source of energy for the cells. Patients with myoadenylate deaminase deficiency do not retain ribose during heavy exercise, so supplementation may be required to rebuild levels of ATP.[13][14]

Creatine monohydrate is also helpful for for AMPD patients, as it provides an alternative source of energy for anaerobic muscle tissue.[15]

Potential Complications

There is an increased risk that statin (cholesterol reducing drugs) will cause myopathy (muscle weakness) in individuals with MADD.[16]

Anesthesia has the potential to cause malignant hyperthermia, an uncontrolled increase in body temperature, and permanent muscle damage in patients with MADD. Individuals with MADD are advised to notify their an anesthesiologist about their condition prior to surgery.[8]

In most where myopathy is present with MADD, a second muscle disease is present and symptoms are worst than either disease in isolation.[17][18]

References

  1. ^ a b c "Adenosine monophosphate deaminase deficiency". Genetics Home Reference. United States National Library of Medicine. July 2008. http://ghr.nlm.nih.gov/condition/adenosine-monophosphate-deaminase-deficiency. 
  2. ^ Sabina, R L; Swain, J L; Olanow, C W; Bradley, W G; Fishbein, W N; Dimauro, S; Holmes, E W (1984). "Myoadenylate deaminase deficiency. Functional and metabolic abnormalities associated with disruption of the purine nucleotide cycle". Journal of Clinical Investigation 73 (3): 720–30. doi:10.1172/JCI111265. PMC 425074. PMID 6707201. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=425074. 
  3. ^ Loh, Evan (2000). "AMPD1 Genotype Predicts Survival in Patients with Heart Failure". Japanese Circulation Society. http://www.j-circ.or.jp/english/sessions/reports/64th-ss/loh.htm. 
  4. ^ Role of nitric oxide in adenosine-induced vasodilation in humans. PMID 9576114. 
  5. ^ "Myoadenylate Deaminase Deficiency". Muscular Dystrophy Association. http://www.mda.org/disease/mad.html. 
  6. ^ Morisaki, H; Morisaki, T (2008). "AMPD genes and urate metabolism". Nihon rinsho. Japanese journal of clinical medicine 66 (4): 771–7. PMID 18409530. 
  7. ^ Belfrage, Måns; Sollevi, Alf; Segerdahl, Märta; Sjölund, Karl-Fredrik; Hansson, Per (1995). "Systemic Adenosine Infusion Alleviates Spontaneous and Stimulus Evoked Pain in Patients with Peripheral Neuropathic Pain". Anesthesia & Analgesia 81 (4): 713–7. PMID 7573999. http://www.anesthesia-analgesia.org/cgi/pmidlookup?view=long&pmid=7573999. 
  8. ^ a b c "Facts About Metabolic Diseases of Muscle". Muscular Dystrophy Association. December 2009. http://www.mdausa.org/publications/PDFs/FactsAboutMetabolicDisease.pdf. 
  9. ^ Li, Xinhui; Bantel, Carsten; Conklin, Dawn; Childers, Steven R.; Eisenach, James C. (2004). "Repeated Dosing with Oral Allosteric Modulator of Adenosine A1 Receptor Produces Tolerance in Rats with Neuropathic Pain". Anesthesiology 100 (4): 956–61. doi:10.1097/00000542-200404000-00028. PMID 15087633. 
  10. ^ Fredholm, Bertil B.; Halldner, Linda; Johansson, Catarina; Schulte, Gunnar; Lövdahl, Cecilia; Thorén, Peter; Dunwiddie, Thomas V.; Masino, Susan A. et al. (2003). "Consequences of eliminating adenosine A1 receptors in mice". Drug Development Research 58 (4): 350–3. doi:10.1002/ddr.10170. 
  11. ^ Adenosine inhibits depolarization-induced Ca(2+) release in mammalian skeletal muscle.. PMID 10567080. 
  12. ^ Lang, Robert (1998). "What is this Adenosine stuff?". Australasian Anaesthesia. ISSN 1032-2515. http://web.squ.edu.om/med-Lib/MED_CD/E_CDs/health%20development/html/clients/WAWFSA/html/papers/pap001.htm. 
  13. ^ Wagner, D.R.; Gresser, U.; Zöllner, N. (1991). "Effects of Oral Ribose on Muscle Metabolism during Bicycle Ergometer in AMPD-Deficient Patients". Annals of Nutrition and Metabolism 35 (5): 297–302. doi:10.1159/000177660. PMID 1776826. 
  14. ^ Zöllner, N.; Reiter, S.; Gross, M.; Pongratz, D.; Reimers, C. D.; Gerbitz, K.; Paetzke, I.; Deufel, T. et al. (1986). "Myoadenylate deaminase deficiency: Successful symptomatic therapy by high dose oral administration of ribose". Klinische Wochenschrift 64 (24): 1281–90. doi:10.1007/BF01785710. PMID 3102830. 
  15. ^ Tarnopolsky, Mark A. (2007). "Clinical Use of Creatine in Neuromuscular and Neurometabolic Disorders". In Salomons, Gajja S.; Wyss, Markus. Creatine and Creatine Kinase in Health and Disease. Subcellular Biochemistry. 46. pp. 183–204. doi:10.1007/978-1-4020-6486-9_10. ISBN 978-1-4020-6485-2. PMID 18652078. http://books.google.com/books?id=HjU1FYjjoRcC&pg=PA182. 
  16. ^ Vladutiu, Georgirene D.; Simmons, Zachary; Isackson, Paul J.; Tarnopolsky, Mark; Peltier, Wendy L.; Barboi, Alexandru C.; Sripathi, Naganand; Wortmann, Robert L. et al. (2006). "Genetic risk factors associated with lipid-lowering drug-induced myopathies". Muscle & Nerve 34 (2): 153–62. doi:10.1002/mus.20567. PMID 16671104. 
  17. ^ Vockley, Jerry; Rinaldo, Piero; Bennett, Michael J.; Matern, Dietrich; Vladutiu, Georgirene D. (2000). "Synergistic Heterozygosity: Disease Resulting from Multiple Partial Defects in One or More Metabolic Pathways". Molecular Genetics and Metabolism 71 (1–2): 10–8. doi:10.1006/mgme.2000.3066. PMID 11001791. 
  18. ^ Sabina, Richard L. (2000). "MYOADENYLATE DEAMINASE DEFICIENCY: A Common Inherited Defect with Heterogeneous Clinical Presentation". Neurologic Clinics 18 (1): 185–94. doi:10.1016/S0733-8619(05)70184-5. PMID 10658174. 

Further reading