Tuesday, September 2, 2014

CPT2 Triggers

The literature is confusing as to what triggers CPT2 episodes.  This article is an attempt to list everything identified as a possible trigger, and to identify the sources that identify it.  Obviously, triggers identified by many different sources are the most likely to be strong triggers.

Additions/Corrections to this list are ongoing.

CPT2 Triggers

Inadequate food consumption
High fat diet
Frequently listed as important in recovery; not recognized in the literature as a trigger. Note: There is some anecdotal support for dehydration being a trigger.
Failure to follow ER Protocol letter (including malpractice in handling a CPT2 patient in the ER)
Psychological stress/anxiety
Lack of sleep/inadequate sleep
--Viral Infection

Extremes in temperature
-- Cold temperature
--Valproic acid
--General anesthesia
--Ibuprofen (Advil/Motrin)
--Diazapam in high doses

CPT2 Triggers based on anecdotal evidence:
Menstrual Period and/or ovulation
"increased pain and stiffness every month prior to period"; "My body gets so stiff before menstruation and I have total weakness during ovulation".
"I had to take it 5 years ago for pneumonia and found that I couldn’t as it increased my metabolism."
Gan Mao Ling
"I took it because it is supposed to reduce illness when taken at onset.  It caused severe cramping in my large leg muscles.  I thought it was a coincidence, and took it again a month later when I thought I was getting sick.  It again caused severe cramping.  I had my CK tested and it was elevated.  I do note that in both cases, my oncoming illness completely stopped right after taking Gan Mao Ling."
High Altitude/Low Oxygen
As CPT2 is a fatty acid oxidation disorder, availability of oxygen may be a factor.  Caution should be used in lower oxygen environments (aircraft, mountains, etc).
Air Travel
From a post on https://www.facebook.com/groups/CptType2 CPT2 episodes appear to be triggered by air travel. As flights are pressurized to around 2500 meters/8000 feet, slight hypoxia may be involved. The stress of air travel might also be a trigger.

Rhabdomyolysis Triggers (Since a primary risk of CPT2 deficiency is rhabdomyolysis, anything that triggers rhabdomyolysis in non-CPT2 patients is something CPT2 patients might want to avoid):
Alcohol  Abuse
Excessive physical exertion, especially in previously untrained individuals ("white-collar rhabdomyolysis")
High Temperature, temperature extremes
Conditions of severe agitation, such as tonicclonic seizures
Direct muscle injury (particularly "crush injury syndrome"
Muscle ischemia (shock, CO poisoning, asthma, arterial thrombosis, vascular occlusion, air emboli, severe sickle cell crisis, prolonged immobilization)
Abuse drugs (cocaine, heroin, other opiates, amphetamines, club drugs like ecstasy, benzodiazepines)
"other drugs/toxins/venoms": Various drugs, such as corticosteroids, immunosuppressants, salicylates, fibrates, antibiotics, chemotherapeutic agents, antidepressants, antipsychotics and anesthetics have been associated with rhabdomyolysis, not only in toxic, but also in therapeutics doses.
Metabolic Endorine Disorders
There are many other events that can infrequently result in rhabdomyolysis

“FOD” (Fatty Acid Oxidation Disorders support group) = https://www.fodsupport.org/cpt2.htm
“CPTDeficiency” (the CTP2 Deficiency Association) = http://www.cptdeficiency.org/inhoud/attack_triggers_inhoud.htm
“Connecticut” (State of Connecticut Genetics Newborn Screening Program): http://www.ct.gov/dph/lib/dph/family_health/newborn_screening/pdf/hpcptii.pdf
“Wikipedia” (Wikipedia page retrieved 9/2/2014):  http://en.wikipedia.org/wiki/Carnitine_palmitoyltransferase_II_deficiency
“NMD” (Neuromuscular Disorders Journal): http://www.nmd-journal.com/article/S0960-8966(01)00228-0/abstract
“CER” (Clin. Exp. Rheumatol.): http://www.ncbi.nlm.nih.gov/pubmed/11579721
“Annals” (Annals of Internal Medicine): http://annals.org/article.aspx?articleid=691984
“Myopathies” (Myopathies, An Issue of Neurologic Clinics by Mazen Dimachkie, page 788): http://books.google.com/books?id=IiA4BAAAQBAJ&pg=PA788&dq=cpt2+triggers&hl=en&sa=X&ei=t10GVNjkMte4ogSBkIL4Ag&ved=0CCwQ6AEwAg (note that this source also identifies MCT oil and Bezafibrate as improving CPT2 symptoms)
“Muscle Disease” (Muscle Disease: Pathology and Genetics by Goebel, Sewry and Wells, page 266): http://books.google.com/books?id=hyC5UvC5cAAC&pg=PA266&dq=cpt2+triggers&hl=en&sa=X&ei=t10GVNjkMte4ogSBkIL4Ag&ved=0CDIQ6AEwAw (note that this source also identifies Bezafibrate as “shown to restore the capacity for normal fatty acid oxidation in muscle cells”, and recommends MCT oil)
“Lipobiology” (Lipobiology by G.J. van der Vusse, page 306): http://books.google.com/books?id=hyC5UvC5cAAC&pg=PA266&dq=cpt2+triggers&hl=en&sa=X&ei=t10GVNjkMte4ogSBkIL4Ag&ved=0CDIQ6AEwAw
"Washington Neuromuscular" (Washington University, St. Louis, MO Neuromuscular Disease Center): http://neuromuscular.wustl.edu/msys/cardiac.html#cpt2 (note: Provides a detailed list of information about CPT2)
"Orphanet" (Orphanet, portal for rare diseases and orphan drugs): http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=157
"Iowa DPH" (Iowa State Department of Public Health): https://idph.state.ia.us/genetics/common/pdf/cpt2.pdf
"Bonnefont" (Carnitine palmitoyltransferases 1 and 2: biochemical, molecular and medical aspects by Bonnefont et al.): http://www.carnevalijunior.com.br/wp-content/uploads/2010/03/cpt2001.pdf
Medlink (Medlink Neurology): http://www.medlink.com/medlinkcontent.asp
"Biomed Research" (Journal of Biomedicine and Biotechnology, Vol. 2010, Article ID 340849): http://www.hindawi.com/journals/bmri/2010/340849/ (also provides an easy to understand description of fatty acid metabolism during exercise)
"New England Journal" (New England Journal of Medicine, Feb. 19, 2009 article by Bonnefont, et al.): http://www.nejm.org/doi/full/10.1056/NEJMc0806334
"Genetic Neuromuscular Disorders" (chapter 64): http://link.springer.com/chapter/10.1007/978-3-319-07500-6_64
"OMIM" (Online Mendelian Inheritance in Man online gatalog of human genes and genetic disorders): http://omim.org/entry/255110
"Hippokratia" ("Rhabdomyolysis updated" article): http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2658796/
"Molecular mechanisms of statin intolerance": https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4889699/
"Ezetimibe-associated myopathy in monotherapy and in combination with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor": https://www.onlinecjc.ca/article/S0828-282X(06)70253-7/fulltext
"Monotherapy with Ezetimibe Causing Myopathy": https://www.amjmed.com/article/S0002-9343(05)00557-7/fulltext
"Worsening mypoathy associated with ezetimibe in a patient with McArdle Disease": https://academic.oup.com/qjmed/article/98/6/461/1548198
"Myopathy induced by statin-ezetimibe combination: Evaluation of potential risk factors": https://academic.oup.com/qjmed/article/98/6/461/1548198
"Product Monograph Sandoz Ezetimibe": https://www.sandoz.ca/sites/www.sandoz.ca/files/Ezetimibe%20Product%20Monograph.pdf

Other notes:

Treatment Protocol: “Glucose remains the mainstay therapy in the management of CPT II deficiency. Intravenous glucose infusions have been shown to be beneficial in improving exercise tolerance, whereas oral glucose has not” (Nature)

Interesting:  “Exercise tolerance is markedly improved by a glucose infusion in patients with CPT II deficiency, but because of lower glucose availability and higher insulin levels that inhibit muscle glycogenolysis, the patients cannot achieve this effect themselves by oral glucose ingestion.” http://www.ncbi.nlm.nih.gov/pubmed/12370460?dopt=Abstract&holding=npg

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