The potential value of red cell transketolase in the metabolic evaluation of disease
Derrick Lonsdale, M.D.
Department of Pediatrics and Adolescent Medicine
Raymond J. Shamberger, Ph.D.
Department of Biochemistry
Transketolase is a thiamine pyrophosphate dependent enzyme, which occurs twice in the hexose monophosphate shunt.1 A number of investigators have used it in assessing intracellular cofactor deficiency, since it occurs in red cells, which are easily obtainable for testing.2–4 Two aspects must be considered in the use of this enzyme as a clinical tool. In the first part of the assay, activity is measured by determining the amount of sedoheptulose-7-phosphate produced per unit of time. By adding thiamine pyrophosphate, the speed of production is measured again. Two values are reported: the initial measured transketolase activity (TKA) and thiamine pyrophosphate percentage uptake (TPP%), sometimes referred to as the thiamine pyrophosphate effect (TPPE).5 Although we have found this enzyme assay to be abnormal in a number of clinical situations for reasons incompletely understood, we have chosen the cases of four children to illustrate an innovative approach that applies a biochemical principle in attempting to study a disease whose clinical expression may reflect defective energy metabolism. The cases chosen have a neurologic background, but do not represent a homogenous disease entity in the traditional manner. All four children were treated with large doses of thiamine hydrochloride; this therapy was based on the results of TKA and TPPE assays, one or other of which was shown to revert to normal after therapy and correlated well with the individual clinical response as well as changes in creatine and creatinine excretion in the urine in the only two patients tested in this manner after the . . .