When a patient reports a significant improvement, it can be tempting for clinicians to ignore follow-up testing. Testing is expensive and may require dietary changes, blood draws, or sample collections that can disrupt daily routines or be challenging for patients.
Follow-up testing to document improvement is not only a best medical practice but on occasion, it can modify the final diagnosis or further adjust a nutritional protocol. Recently, I consulted with a clinician on pre/post Organic Acids (OAPs) regarding a 6-year-old child with developmental delays who do not use any pharmaceutical medications.
The patient’s initial presentation included:
- Constipation and painful defecation
- Irritability and defiance
- Developmental disorder (undiagnosed) with speech and motor apraxia (difficulty performing desired learned, skilled movements)
- Scoliosis supported by a brace
The clinician immediately ordered food sensitivity testing and then the Organic Acids profile. While waiting for the OAP results to come back the patient discontinued wheat, corn, and dairy based on the food sensitivity results. The clinician also increased healthy fats and hydration. The food eliminations and diet changes significantly improved constipation and defecation but had little effect on the apraxia.
The OAP results indicated significant dysregulation of the patient’s biochemical and mitochondrial function. Dysregulation of biochemistry and/or mitochondrial function can result from an inheritance, environmental exposures, psychological stress, or poor nutrition. Biochemical pathways can be overwhelmed by too many calories (over-nutrition) or starved if the proper nutrient cofactors are unavailable in the diet. Inflammation and dysregulation result from either dietary choice and the dysregulation is reflected in the OAP results. An Environmental Pollutants profile (EPP) collected simultaneously with the Organic Acids profile indicated recent exposures to styrene, phthalates, parabens, xylene, and MTBE (gasoline additive).
A protocol was designed after this first Organic Acids test and the child made significant improvements in speech and movement and started to catch up on developmental milestones. The OAP test indicated additional nutritional supports, including:
The chemical exposures were tracked down to the food served on plastic dishes and eliminated, and the patient was supported with a gentle detoxification protocol. Once these corrections were in place the child began to improve in energy level, and muscle tone (posture). She began speaking in full sentences and started counting. She also learned to write her name and draw recognizable images instead of scribbles.
After a few months of growth and improvement, however, the child plateaued; she began to experience fatigue again in June/July 2022, began finger-sucking, and experienced knee pain when running. At the visit, the mother reports that the patient has been primarily eating carbohydrates.
A second OAP was ordered, and the results were significantly different due to the corrective protocol applied after the first results. However, while biochemical and mitochondrial function were improved overall, there were several significant findings that potentially explain the child’s developmental plateau, and another, different, toxic exposure has become apparent. Biochemical findings included:
- An apparent inability to convert carbohydrates into pyruvate. Poor conversion may raise blood/brain glucose levels (metabolic syndrome).
- An elevated fumarate is unlikely on a high-carbohydrate diet. Genetic defects in the enzyme fumarase are well documented and are associated with developmental delays.
- A problem in the b-oxidation cycle converting fat into citrate, the first step in the ATP-producing Citric Acid Cycle.
- High levels of the nutritive ketone body beta-hydroxybutyrate are unexpected with a high-carbohydrate diet. If they are beyond the detection limit, the ketones are very high, and may not be breaking down properly to produce energy.
- Very low levels of the serotonin metabolite 5-hydroxyindolacetate and the tryptophan bacterial metabolite 3-indole
- Increased levels of the Fusarium mold biomarker tricarballylate (above).
Using information from US BioTek’s Organic Acids Interpretation guide we learn:
- Low pyruvate may be associated with fasting or low-calorie intakes, malabsorption, or dysfunction of the glucose-processing pathways. If glucose cannot be converted into pyruvate, blood glucose levels may rise.
- High fumarate levels may be genetic. Individuals with genetic fumarase defects often improve on low-carbohydrate diets. It is important to rule out other potential causes of fumarate elevations, which include hypoxia (sleep apnea), kidney problems, or high intakes of the amino acid tyrosine or its precursor phenylalanine.
- Beta-oxidation is the primary fatty acid pathway in the liver. This pathway breaks down long-chain and other fatty acids so they can be converted and ultimately used to produce ATP. Normal b-oxidation will increase or maintain citrate levels. An L-carnitine deficiency can inhibit normal beta-oxidation and promote omega-oxidation, increasing adipate and suberate levels. Other nutrients are also required to completely support the pathway.
- Synthesis of beta-hydroxybutyrate and other ketones may be increased by hormones such as cortisol, insulin, glucagon, thyroid, etc. Nutrient deficiencies or an unbalanced diet may also increase ketone levels.
- The metabolite 5-hydroxyindoleacetate is created during serotonin breakdown in the central and peripheral nervous system. The metabolite 3-indoleacetate is created in the gut from the bacterial metabolism of tryptophan. However, tryptophan may be the precursor for two other metabolites on the results - quinolinate and kynurenate, which are created on a different biochemical pathway. Fatty vitamin status and inflammation levels can dictate which pathway uses available tryptophan.
- Tricarballylate is synthesized from simple carbohydrates metabolized primarily by coli bacteria. It is then absorbed into the circulation and excreted by the kidneys. Exposure to Fusarium molds either through grains or as an aeroallergen may increase tricarballylate levels.
The patient’s protocol was further adjusted and as of October 2022, the mother reports that the patient is now able to keep pace with the family on hikes, is writing her name even better and more legibly, and that the patient’s scoliosis remains stable due to the patient’s improved strength and muscle tone.
Action steps for each of these analytes can be found in US BioTek’s Organic Acids Interpretation guide. Using the information from the guide, can you craft a protocol to support this patient?
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