High Amino Developmental Delay

Summary

A combination of environmental, nutritional, and genetic metabolic weaknesses were found as potential causative factors in the failure of neurological development for this 2-year-old girl. Vitamin B6 insufficiency, arsenic exposure, and intestinal dysbiosis are key features in the initial laboratory workup.

This content was created by the Metametrix Institute

History

This two-year-old had been evaluated as non-autistic with motor developmental delay. She had difficulty standing and no progress with walking. Both parents were very engaged in providing dietary and environmental assurances for health.

Age

2

Gender

Female

Description of Results

A urine mineral profile after DMSA challenge showed very high arsenic.

All other toxic metals were well below reference limits and nutrient elements were somewhat elevated, as expected under the influence of the chelator challenge.

Plasma amino acids showed significantly high levels of leucine, isoleucine, valine, lysine, and tyrosine, with all other essential amino acids in high normal ranges. This pattern suggests difficulty utilizing amino acids that may be due to insufficiency of vitamin B6. The metabolic markers for B6, xanthurate and kynurenate were both highly elevated, confirming a need for aggressive repletion of vitamin B6.

In addition to low EPA with high arachidonic acid, the plasma fatty acid profile also reveals a pattern consistent with medium-chain fatty acid oxidation difficulty. The 12- and 14-carbon saturated and monounsataurated fatty acid members are high. Even the lower chain length odd numbered fatty acids are elevated while the long-chain members are below reference limits. In light of these findings, the finding of high suberate and very high ethylmalonate in urine takes on significance as indicators that carnitine and riboflavin may help overcome fatty acid oxidation deficits.

Other vitamin specific markers in urine show need for biotin, vitamin B12, and folate. Strongly elevated glutathione production is shown by concurrently elevated pyroglutamate, sulfate, and alpha-hydroxybutyrate.

Multiple strain bacterial overgrowth is indicated by the presence of six bacterial metabolic products at high levels, including three bacterial in the tenth patient population decile. Two yeast markers are likewise in the tenth decile.

Recommendations

Start micronutrients: B6, biotin, B12, folate, carnitine, coenzyme Q10, trace elements, and vitamin C.

Do confirmatory arsenic toxic burden testing such as a repeat urine challenge or hair mineral test. Implement arsenic reduction procedures on confirmation of body burden elevation.

Follow up with organic acid retesting in 90 days to confirm adequacy of B6 supplementation, to check progress in resoring orthobiosis, and to monitor glutathione status.

Other Comments

The key factor that emerges from this evaluation is vitamin B6 insufficiency. This difficulty is exacerbated by multiple nutrient needs and detoxification demands. It is difficult to know how arsenic toxicity might manifest in such a case. The parents are unaware of any acute arsenic exposure, but such is indicated by the fact that only arsenic is greatly elevated in urine, while other toxic elements in urine and in erythrocytes are in normal limits. Up-regulation of hepatic detoxification is likely to be in response to organic toxins such as the microbial products rather than to effects of arsenic. However, a high body burden of arsenic will hamper normalization of neurological development. The general state of metabolic distress is reflected in the high levels of urinary products from epinephrine, norepinephrine, dopamine and serotonin seen in the elevated vanilmandelate, homovanillate, and 5-hydroxyindoleacetate in the profile of organic acids.