Biology of Disease

supported by anthropometric measurements, coupled with a sympathetic

psychological assessment.

Vitamins

The majority of vitamin disorders encountered in clinical practice are

deficiencies. The investigative procedures are varied and depend upon

the vitamin in question. Chemical tests can help to confirm the diagnosis

of overt vitamin deficiencies and may enable diagnosis to be made at a

relatively early stage. The types of tests used include direct measurements of

the concentration of the vitamin or one of its metabolites in plasma, serum,

erythrocytes, urine or tissue biopsies. The concentration of vitamin in plasma

does not necessarily reflect body vitamin status and a measurement of the

concentration in blood cells may be a better indicator. Enzyme-based tests

are available for some vitamins. Metabolites that accumulate in the blood

or urine following the blockage of a metabolic pathway normally catalyzed

by an enzyme that requires a vitamin as a cofactor or coenzyme may also be

investigated.

Vitamin B 1 (thiamin) deficiency can be assessed by direct measurement

of its concentration in plasma or indirectly by determining the increase in

erythrocyte transketolase activity in the presence of added TPP. The increase

in activity is called the activation coefficient. A coefficient less than 15% is

considered normal; an increase of 15–25% indicates a marginal deficiency,

while an increase greater than 25% with clinical signs is indicative of severe

thiamin deficiency. Thiamin deficiency can also be assessed by the clinical

response to administered thiamin, that is, an improvement in the condition

after administering thiamin supplements. The nutritional status of vitamin B 2

(riboflavin) is investigated in a similar manner by determining the activation

of glutathione reductase activity of erythrocytes in the presence of added

FAD.

Assessing the nutritional status of niacin is more difficult. The usual method

is to determine the concentrations of metabolites of niacin, for example

1-methylnicotinamide and 1-methyl-3-carboxamido-6-pyridone, in urine

samples. Both are reasonably good measures of niacin status, as is the ratio of

the concentrations of NAD+ to NADP+ in erythrocytes. A ratio of less than 1.0

may identify subjects at risk of developing a niacin deficiency. The nutritional

status of vitamin B 5 (pantothenic acid) can also be assessed by determining

its concentration in plasma or urine samples. In general, plasma pantothenic

acid concentrations decrease in patients on a pantothenic acid deficient diet.

However, the concentrations of pantothenic acid in blood respond less readily

to intake than does the concentration in urine.

The status of vitamin B 6 can be investigated in a manner similar to those for

thiamin and riboflavin by determining the activation coefficients of erythrocyte

alanine and aspartate transaminase activities (ALT and AST respectively) in

the presence of the cofactor pyridoxal phosphate. Alternatively, vitamin B 6

status may be assessed by the tryptophan loading test. Tryptophan is normally

catabolized by the pathway shown in Figure 10.38. However, the activity of

kynureninase decreases markedly in B 6 deficient patients. If such a patient

is given an oral dose of 50 mg per kilogram body weight of tryptophan, then

there is an increase in the amounts of kynurenic and xanthurenic acids formed

and these appear in the urine. Generally less than 30 mg of xanthurenic acid

is excreted daily; higher amounts are indicative of vitamin B 6 deficiency.

However, some other disorders of tryptophan catabolism can also lead to an

increase in xanthurenic acid production so abnormal results must be treated

with caution.

A possible deficiency of vitamin H (biotin) can be investigated by measuring

its concentration in whole blood, serum or urine. Determining plasma biotin

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