• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To register, simply click the Register button at the top right.

Maltese et al: Genetic evaluation of AMPD1, CPT2, and PGYM metabolic enzymes in patients with CFS


Senior Member
Genetic evaluation of AMPD1, CPT2, and PGYM metabolic enzymes in patients with chronic fatigue syndrome

Maltese PE1, Venturini L2, Poplavskaya E3, Bertelli M4, Cecchin S4, Granato M4, Nikulina SY3, Salmina A3, Aksyutina N3, Capelli E5, Ricevuti G2, Lorusso L6.
  1. MAGI Non-Profit Human Medical Genetics Institute, Rovereto, TN, Italy paolo.maltese@assomagi.org.
  2. Cellular Pathophysiology and Clinical Immunology Laboratory, Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.
  3. Department of Internal Diseases N.1, Krasnoyarsk State Medical University, Krasnoyarsk, Russia.
  4. MAGI Non-Profit Human Medical Genetics Institute, Rovereto, TN, Italy.
  5. Immunology and Genetic Analysis Laboratory, Department of Earth and Environmental Sciences, University of Pavia, Pavia, Italy.
  6. Department of Neurology, Mellino Mellini Hospital, Chiari, BS, Italy.
Genet Mol Res. 2016 Jul 29;15(3). doi: 10.4238/gmr.15038717.


Chronic fatigue syndrome (CFS) is a disease that can seriously impair one's quality of life; patients complain of excessive fatigue and myalgia following physical exertion.

This disease may be associated with abnormalities in genes affecting exercise tolerance and physical performance.

Adenosine monophosphate deaminase (AMPD1), carnitine palmitoyltransferase II (CPT2), and the muscle isoform of glycogen phosphorylase (PYGM) genes provide instructions for producing enzymes that play major roles in energy production during work.

The aim of this study was to look for evidence of genotype-associated excessive muscle fatigue.

Three metabolic genes (AMPD1, CPT2, and PYGM) were therefore fully sequenced in 17 Italian patients with CFS. We examined polymorphisms known to alter the function of these metabolic genes, and compared their genotypic distributions in CFS patients and 50 healthy controls using chi-square tests and odds ratios. One-way analysis of variance with F-ratio was carried out to determine the associations between genotypes and disease severity using CF scores.

No major genetic variations between patients and controls were found in the three genes studied, and we did not find any association between these genes and CFS.

In conclusion, variations in AMPD1, CPT2, and PGYM genes are not associated with the onset, susceptibility, or severity of CFS.

Pretty impressive that they chose specific targets on a rational basis (ie, paying attention to our unique symptom), and did full exon sequencing. But it's odd that they used Fukuda and didn't require (or even ask about) PEM.

They did find some enzyme-altering mutations in the CFS patients, but they also found them in the controls. They were a bit more prevalent in the CFS patients, but not enough to be statistically significant. If they were able to reproduce the study with a larger sample, it's possible those differences would be significant. But in any event, the odds ratios are fairly low - so at most the mutations would be associated with a small increase in the risk of developing CFS, and certainly would not be causative of CFS.

This bit is potentially interesting:
ANOVA revealed that EBV-negative patients demonstrated significantly higher CF scores (F-ratio = 6.16, P = 0.02) as compared to those with a history of mononucleosis (high levels of IgG or IgM antibodies for EBV in their last blood test) (Figure 1).

Anyhow, it looks like a pretty good study. Hopefully they stay interested in the disease, and do some more research. But with better criteria or mandatory PEM! :D
Last edited:


Senior Member
Silicon Valley, CA
Other studies have observed that patients whose symptoms start with EBV are more likely to recover, or more likely to regain some function. It's interesting to have that confirmed again... if I'm following you, @Valentijn


Senior Member
Northern California
I recently learned about carnitine palmitoyl transferase II deficiency, myopathic form, so I did a search for CPT2 on Phoenix Rising and was pleasantly surprised to find the paper that @mango posted several years ago.

If your symptoms align, it's certainly worth getting checked out for because the treatment is simply a change in diet.

Here's a link to learn more about CPT2 and a link to a single genetic test a available through Invitae.