copper, selenium and molybdenum deficiencies can contribute
to disease. Trace element deficiencies are most commonly due
to inadequate intake or to intestinal disease reducing absorp-
tion; treatment is with adequate replacement.
The features of copper and zinc deficiencies are summar-
ized in Table 35.1.
FURTHER READING AND WEB MATERIAL
Ahmed FE. Effect of diet, life style, and other environmental/chemo-
preventive factors on colorectal cancer development, and assess-
ment of the risks. Journal of Environmental Science and Health. Part C,
Environmental Carcinogenesis and Ecotoxicology Reviews2004; 22 :
91–147.
van Poppel G, van den Berg H. Vitamins and cancer. Cancer Letters
1997; 114 : 195–202.
Bender DA. Nutritional biochemistry of the vitamins. Cambridge:
Cambridge University Press, 1992.
Fitzgerald FT, Tierney LM. Trace metals and human disease. Advances
in Internal Medicine1984; 30 : 337–58.
Useful websites: http://www.nlm.nih.gov/medlineplus/vitamins, http://www.
indstate.edu/thcme/mwking/vitaminsTRACEELEMENTS 269Table 35.1:Common trace element deficiencies
Element Clinical features of Biochemical activity Normal serum/tissue Other comments
deficiency concentration
Copper Osteoporosis, Major enzyme Plasma copper Premature babies
costochondral dysfunction (e.g. (12–26 mol/L) does are predisposed to
cartilage cupping and cytochrome oxidase) not reflect tissue copper deficiency,
anaemia/leukopenia. copper status well as copper stores
Menke’s syndrome Reduced red cell are built up in late
in children superoxide dismutase pregnancy
activity is a better
indicator
Zinc Skin rash, At the active site Serum zinc Adverse effects
hair thinning, diarrhoea, of glutathione 5.6–25μmol/L of zinc include
(acrodermatitis peroxidase and dyspepsia and
enteropathica); protects against abdominal pain
mental apathy and oxidant stresses
impaired T-cell functionCase history
A 24-year-old woman with epilepsy is well controlled on
phenytoin. Months after starting treatment, she complained
of fatigue. Her haemoglobin was 8.0 g/dL and mean corpus-
cular volume (MCV) was 103 fL.
Question
What additional investigations would you undertake?
What is the most likely diagnosis and how should you treat
this patient?
Answer
This patient has a macrocytic anaemia. Your investigations
show her serum folate to be low, with a normal B 12. This con-
firms your suspicion of phenytoin-induced folate deficiency.
A dietary assessment reveals an adequate folate intake;
there is no evidence of other causes of malabsorption.
Phenytoin commonly causes folate deficiency, impairing the
absorption of dietary folate by inducing gastro-intestinal
enzymes involved in its catabolism. Treatment should con-
sist of daily oral folate supplementation, keeping her on
the phenytoin (as this has controlled her epilepsy), and fur-
ther monitoring of her haematological status for response.
During follow up, she should also be monitored for possi-
ble development of osteomalacia (suggested by proximal
myopathy with low serum phosphate and calcium and
raised alkaline phosphatase), as phenytoin also induces the
metabolic inactivation of vitamin D.