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Biotin & Detoxification Needs in Cognitively Delayed Adult


Biotin deficiency may be linked to hyperlipidemia and up-regulated fatty acid desaturation in this mildly psychotic man.

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This aggressive, cognitively delayed 24-year-old male has had many hospitalizations for bowel obstruction and a history of multiple antibiotic courses. He had viral meningitis at 3 months old.





Description of Results

Erythrocyte mineral levels are within normal limits. The pattern of low amino acids includes the glutathione demand pattern of low methionine,threonine, glycine, and serine. A neuroexcitatory and potentially neurotoxic elevationof glutamic acid is found with the normal offsetting decrease of glutamine.

Even though serum antioxidant vitamins are normal, lipid peroxides are extremely elevated, consistent with elevated cell membrane content of polyunsaturated fatty acids.

Plasma fatty acids reveal very high polyunsaturated fatty acids (PUFA) along with the general elevation characteristic of hypertriglyceridemia. The saturated and monounsaturated members are uniformly very high as is generally found when blood lipoproteins (primarily LDL) are elevated.

In the polyunsaturated families, note the normal eicosapentaenoic acid (EPA) with greatly elevated docosahexaenoic acid (DHA) and the normal linoleic acid (LA) with high gamma linolenic acid (GLA) and very high docosatetraenoic acid. These patterns show a stimulationof desaturase enzyme activity.

Desaturase stimulation is confirmed by extreme elevation of the endogenously produced mead acid that is normally present only in very low concentrations.

Note aso the severe elevation of the 15- and 17-carbon odd chain fatty acids.

This patient is showing stimulation of liver fatty acid desaturase activity along with stimulation of odd-chain fatty acid synthesis such as found due to the build up of propionic acid. The three factors that might contribute to propionate build up are deficiencies of biotin or vitamin B12, and increased production by intestinal bacterial populations. These factors can be assessed by examination of the Organic Acids profile.

Although most intermediates of amino acid metabolism on the first page of the Organic Acids profile are in or near their normal limits, b-hydroxyisovalerate is quite elevated, indicating insufficiency of biotin to maintain the catabolic pathway of L-leucine. This biochemical marker signals difficulty in all biotin-dependent pathways, including the conversion of propionate to succinate. Therefore, we have a confirmation of biotin insufficiency as a cause of several abnormalities found in the plasma fatty acid profile. In addition, we can surmise that, if this situation has been present chronically due to childhood events or genetic factors, the neurological effects of biotin deficiency may have contributed to the cognitive impairments in this case.  Mutations in the biotinidase gene occur with a relatively high frequency, and they can be treated effectively with pharmacologic doses of biotin.

Hepatic detoxification impairment is indicated in two ways. First, the elevated a-hydroxybutyrate signals attempts to up-regulate hepatic glutathione production in response to the oxidative challenge. At the same time total glutathione status is depleted as shown by the quite low urinary sulfate. Greatly elevated benzoate draws further attention to impaired hepatic detoxification as glycine conjugation is inadequate for the demand.

The organic acid sulfur metabolism observations, linked with the plasma amino acid pattern show a strong need for support of sulfur amino acids and glycine/threonine that allow synthesis of glutathione.



Other Comments

Biotin deficiency has been linked to increased accumulation of odd-chain fatty acids due to decreased activity of propionyl-CoA-carboxylase. We may be finding in this patient a combination of biotin deficiency effects and other factors that are stimulating the fatty acid desaturase enzymes, producing such unusually high levels of several PUFAs.