Biochemical Identification of the Carrier State in Tay-Sachs'Disease. ∗

Abnormally elevated levels of various glycolytic, dehydrogenating and transaminating enzymes have been previously demonstrated in sera and spinal fluids of infants with Tay-Sachs'disease (TSD) (1,2). These elevated concentrations, however, were regarded as reflections of the secondary tissue degenerations inherent to the disorder and were not considered to be an indication of any fundamental metabolic defect. Since the disease has been clearly proven to be a hereditary disorder transmitted through an abnormal autosomal recessive gene, parallel enzyme determinations were also performed upon a group of parents of the afflicted children. No analogous serum enzymatic changes were noted in the parents, although it was observed that levels of fructose-1,6-diphosphate aldolase (F-1,6-DPA) were frequently in the low range of normal. These mildly depressed values suggested the need for more specific analysis of serum aldolase and prompted the current study of a closely related enzyme, fructose-1-phosphate aldolase (F-1-PA).

Fructose-1,6-diphosphate is used as the substrate in determination of serum aldolase. It has been shown that F-1-PA may also catalyze the breakdown of this substrate, but at a diminished velocity(3,4). What is conventionally referred to as F-1,6-DPA concentration therefore is a measurement of both F-1,6-DPA and F-1-PA activity, predominantly the former (5). When fructose-1-phosphate serves as the substrate, only F-1-PA produces cleavage to trioses(5). A postulated absence of circulating F-1-PA might result in a small reduction of serum aldolase (fructose-1,6-diphosphate substrate) but would be unmasked only in a system utilizing fructose-1-phosphate. While F-1-PA is sometimes designated as “liver'aldolase, it is nevertheless present in some measure within all normal tissues and serum (6).

The present report is concerned with the serum levels of aldolase as measured by these 2 substrates in 15 patients with confirmed TSD and 114 parents, siblings and other relatives of these infants.