A reader forwarded the results of Organic Acid Tests done by Quest Diagnostic Biochemical Genetics lab. They had several abnormal results and was frustrated because their MD did not know what to do with it! In theory, it would indicate genetic mutations — in theory, but to more confident, explicit DNA testing would be needed (which is also fuzzy for interpretation).
“Approximately one thousand inborn errors of metabolism (IEM) have been identified to date primarily through the detection of endogenous metabolites abnormally accumulated in biological fluids and tissues. The laboratory discipline that covers the biochemical diagnosis of IEM is Clinical Biochemical Genetics, and is defined as one concerned with the evaluation and diagnosis of patients and families with inherited metabolic disease, monitoring of treatment, and distinguishing heterozygous carriers from non-carriers by metabolite and enzymatic analysis of physiological fluids and tissues.” [MayoClinic]
When we come to CFS patients — there is (IMHO) a significant risk of misidentifying an abnormality as being genetic instead of being due to a microbiome shift. There are several roads to go down:
- You do not have CFS proper, you have a metabolic error
- You do have CFS, and the abnormality is due to the microbiome shift
- You have a metabolic error that predispose you to CFS, because over and under production of organic acids encourages a shift of the microbiome
Reviewing the literature, there is not sufficient knowledge to know which is true. We do know that DNA SNPs are associated with CFS, FM, IBS and MCS. Checking each of the thousand metabolic errors for relevant SNPs and then seeing if there are any matches with the above DNA SNPs is a massive amount of work and likely have informational value only (I am concerned about treatment value – so doing such, honestly, does not interest me).
With that said, let us see what we can find.
The Unusual Results
- N-Acetylaspartic: High
- 2-Hydroxyglutaric: High (1 over)
- Citric: Low
- 3-Hydroxyisobutyric: Low
- 2-Hydroxisovaleric: Low
- Ethylmalonic: Very High
- Methylsuccinic: High
- Glutaric: Low
- Adipic: High
The first step is always to try googling/wikipedia each item. I actually found wikipedia very sparse. The HMDB provides much more information — and are linked below. The information is “thick”, suitable for professionals above MD pay grades!
- N-Acetylaspartic acid is a derivative of aspartic acid. It is the second most concentrated molecule in the brain after the amino acid glutamate. It is synthesized in neurons from the amino acid aspartate and acetyl coenzyme A. The various functions served by N-acetylaspartic acid are still under investigation, but the primary proposed functions include:. 1) A neuronal osmolyte that is involved in fluid balance in the brain 2) A source of acetate for lipid and myelin synthesis in oligodendrocytes, the glial cells that myelinate neuronal axons 3) A precursor for the synthesis of the important neuronal dipeptide N-acetylaspartylglutamate 4)N-Acetylaspartic acid may also be involved in energy production from the amino acid glutamate in neuronal mitochondria. —
2-Hydroxyglutaric: High (1 over)
- This inhibitory effect leads to alterations in the hypoxia induced factor (HIF)-mediated hypoxic response and alterations in gene expression through global epigenetic remodeling. The net effect is that D-2-hydroxyglutarate causes a cascading effect that leads genetic perturbations and malignant transformation.
Ethylmalonic: Very High
- Ethylmalonic acid is identified in the urine of patients with short-chain acyl-coenzyme A dehydrogenase deficiency, which is a fatty acid metabolism disorder.
- clinically characterized by neuromotor delay, hyperlactic acidemia, recurrent petechiae, orthostatic acrocyanosis, and chronic diarrhea
- Increasing lysine intake may help raise
- Adipic acid in the urine and in the blood is typically exogenous in origin and is a good biomarker of jello consumption. In fact, a condition known as adipic aciduria is actually an artifact of jello consumption (PMID: 1779643 ). However, certain disorders (such as diabetes and glutaric aciduria type I.) can lead to elevated levels of adipic acid and other dicarboxcylic acids (such as suberic acid) in urine. – stop eating Jello????
The Genetic Lab’s Conclusion
“The Pattern of Elevated Organic Acids does not suggest a specific inherited metabolic disorder” – So while there many reading that are off, the pattern does not match what is known — and thus there is no known treatment (since there is not a known problem!).
IMHO, the above tests have very limited treatment information. Association with causes (beyond DNA mutations) or effective treatment is just not there. It is totally unclear if some of these highs and lows are related to bacteria shifts (instead of DNA).
A simple example for 2-Hydroxyglutaric, “High levels of 2-hydroxyglutarate dehydrogenase were found exclusively in organisms that use the hydroxyglutarate pathway. The data indicate that only two pathways are involved in the fermentation of glutamate by the bacteria analyzed. The methylaspartate pathway appears to be used only by species of Clostridium, whereas the hydroxyglutarate pathway is used by representatives of several genera.”