Case Study - Metametrix Clinical Laboratory

History
This child initially presented at 4 years old with a history of multiple ear infections in the first year of life and regression of speech following MMR @ 12 months. He had severe gas and diarrhea prior to implelmenting a gluten and casein-free diet. Cod liver oil had been started before the first ION report which is described below.

An outcome of the initial workup (see Initial ION data below) was to start a custom nutritional supplement containing vitamins B1, 2, 3, and 6, folate, methylcobalamain, vitamins C, D and E, and minerals Mg, Fe, and Zn. The powder was taken twice daily. Cod liver oil was discontinued and borage oil (1gm) and flax oil (1gm) was started along with extra vitamin A at 10000 IU daily. In addition , antifungal medications and a probiotic preparation were used. No supplemental amino acids were used.

On follow up examination after 6 months, the patient appears thin and pale. The mother reports very satisfactory improvement in language and socialization, and good development of self-feeding with improvement in appetite, but she says there seems to be something that is not right. He frequently wakes up sweating and distraught. She also reported an apparent viral infection because of a 48 hour fever that broke spontaneously. This episode occurred only 5-6 days before the specimens were taken for the follow up ION profile testing.

Description of Results
The initial ION report revealed very low zinc with other low trace elements. Serum antioxidant levels were low and serum lipid peroxides were strongly elevated. Mid-normal EPA and DHA with low ALA, GLA, and DGLA prompted adjustment in dietary essential oil supplementation. The organic acid profile suggested mild B-complex insufficiency and a combination of bacterial and yeast overgrowth.

Some favorable shifts in the 6 mo ION follow up test were the finding that erythrocyte zinc had risen from 4.4 to 5.3, and there were slight improvements in magnesium and vanadium. Lipid peroxides showed marked improvement, dropping from 1.4 to 0.4 while serum antioxidant concentrations generally fell in spite of supplementary intake.

The follow up ION results were worse in several aspects. Plasma glutamic acid had risen from 36 to 161 uM and glutamine had dropped from 490 to 336 uM while most essential amino acids were significantly lowered. Plasma omega 3 fatty acids had dramatically declined with only slight improvements found in omega 6 essential fatty acids.

The most compelling evidence for the nature of the changes was found in the urine Organix profile where quinolinate had risen from 2.3 to 30.5 umole/mg creatinine. Concurrent dramatic increases in all neurotransmitter turnover rates were seen in the elevation of the catabolic products. Hepatic detoxification conjugation pathways were overwhelmed because urinary benzoic acid was greatly elevated. Ammonia clearance was also challenged, seen in elevations of orotate and isocitrate. Elevation of bacterial products indicate that a significant source of ammonia is intestinal bacterial growth.

Recommendations
Start supplementation with custom-balanced essential amino acids, and shift to EPA-DHA enriched omega-3 oils. Consider antiviral agents and increase pro-biotic use. Continue to supplement b-complex vitamins, although a transition from the custom-blended product to a standard multi-vitamin might be adequate.

Continuation of relatively aggressive use of vitamin A is mandated by the drop in serum levels on the recent testing of serum vitamins and the evidence of viral or microbial infection. However, the drop in serum concentration may have been an acute response to infection, so continued monitoring of vitamin A is advised while the aggressive supplementation is done.

Other Comments
This case represents the developmental responses frequently found in children when micronutrient deficits are corrected in the early stages of developmental delay. However,the progress was complicated by infections and possible hyperactive immune reactions.

At the follow-up testing, this child was found in a post-infectious state while transitioning in nutrient sufficiency status. It is difficult to sort out the various factors of immune system stress and nutrient intake variables to know the true essential nutrient status, but it is clear that insufficiencies of essential amino acids and essential fatty acids needs correction. The shift in the glutamate/glutamine ratio indicates a catabolic metaboli state.

The epinephrine, dopamine, and serotonin output increases are suspected to be a response to interferon-gamma-stimulated macrophage activation. The latter is strongly indicated by the great elevation of quinolinic acid. We also note the complete lack of response for other kynurenic pathway intermediates reflected by kynurenic and xanthurenic acids being actually lower than on the initial testing. This implies that the quinolinate elevation is not due to simple hepatic tryptophan clearance, and that the vitamin B6 supplementation had successfully loaded hepatic enzymes. It leaves macrophage stimulation as the only explanation of a quinolinate of 30.5, and the delay of several days from fever to specimen for testing tells us something about the persistence of the interferon-macrophage stimulation. Along with the agonistic effect of quinolinate on NMDA receptors, we note the jump of glutamate from low-normal to high concentration in plasma. Since glutamate is the neurotransmitter that activates NMDA receptors, the quinolinate effect may be further exacerbated by shifts in amino acids. This kind of physiological stress has multiple negative impacts on nutrient status, and it is important to assure adequate intake in the recovery period to prevent other developmental delays.

A unique opportunity for insight regarding the long-term metabolic consequences of a viral infection is provided. The specimens for the follow up tests were collected some 5-6 days following the end of the 48 hour high temperature indicative of active immune challenge. So the changes seen in these profiles are apparent persistent metabolic effects following the initial clinical signs of infection.

Finally, note the profound pattern of glutathione up-regulation and demand. Low plasma methionine and homocysteine are accompanied by high a-hydroxybutyrate, high pyroglutamate, and low sulfate, strongly indicating that this child has depleted total body glutathione with ongoing elevated hepatic synthesis signals. In summare, it appears that the initially depleted state has been significantly worsened in specific areas due to response to viral infection. Aggressive support of glutathione and other hepatic detoxification, omega-3 fatty acids, antioxidants, trace elements, and amino acids is needed.

To the degree that the child can tolerate nutrient supplementation, indicating assimilation is preceding normally, we expect gradually improving immune resistance to viral infections and restoration of other tissue responses, including brain development with enhanced neuronal plasticity.

Lab Data

Figure . Initial ION Quin-Autism 02eMin.gif