Biochemical Abnormalities in Hereditary Diseases

Abstract

Recent success in growing human cell lines in culture from skin biopsies of patients with inborn errors of metabolism furnishes an important new technique for study of somatic cells with specific genetic defects. Cell lines from the skin of galactosemic or acatalasic individuals maintain the enzymatic defect characteristic of these metabolic diseases. Galactosemic cell lines grow well in a medium containing glucose but not in one containing galactose. They are unable to metabolize galactose. Cell lines from an acatalasic donor have no detectable catalase activity. Cells from an individual presumed to be heterozygous for this disease maintain catalase activity levels about/half those of normal cell lines, even through multiple subcultures. Some of the future problems in the biochemical-genetic aspects of human hereditary metabolic diseases which may be investigated employing these cell lines in culture are discussed. Two other examples of biochemical abnormalities in hereditary metabolic diseases are presented. It has been shown that the enzyme, phenylalanine hydroxylase, which is missing in patients with phenylketonuria, may also be temporarily deficient in some newborn infants. The temporary deficiency is due to a delay in the expression of the enzyme rather than its congenital absence. This variation in expression of the enzyme should be appreciated in diagnosing phenylketonuria in early infancy. The second example concerns the biochemical abnormality in gout, hyperuricemia. Evidence is presented that gout may arise from more than one hereditary cause. The hyperuricemia in some gouty subjects is primarily of renal origin, while in other gouty subjects it is primarily from the overproduction of uric acid.