Confirmatory studies in the prenatal diagnosis of sphingolipidoses.

Abstract

Extract: Chemical and biochemical variables of the sphingolipids were examined in fetal liver, kidney, and brain using saline-aborted (SA) and hysterotomy-aborted (HA) tissues. Brain sphingolipid hexose (BSH) and ganglioside N-acetyl neuraminic acid (NANA) content were similar in each group (BSH/SA, 4.1–5.0 mg/g dry wt and HA, 3.0–6.7 mg/g dry wt; NANA/SA, 1.1–3.3 mg/g dry wt and HA, 1.3–3.1 mg/g dry wt). The distribution of the major gangliosides was also comparable in each group. Sulfatide levels were lower in the hysterotomy group (0.2–0.4 mg/g dry wt) than in the saline group (0.5–0.9 mg/g dry wt), perhaps reflecting the earlier gestational age of this group. Activities of arylsulfatase A (ARA), β-galactosidase, and hexosaminidase A from each tissue were similar, respectively, in saline-and hysterotomy-aborted fetuses. The ARA activity (liver, 23–67; kidney, 13–21; and brain, 1–42 nmol cleaved/mg protein/hr) was about 10–20% of postnatal levels. Utilizing these control values, amniocentesis-derived diagnoses were confirmed in two fetuses with Tay-Sachs disease (TSD) and in another with Gm1 gangliosidosis type I. The disease-specific ganglioside (Gm2 in TSD and Gm1 in Gm1-gangliosidosis) was significantly elevated in brain from each case (TSD, 5–6 times control values and Gm1-gangliodosis, approximately twice control values). In liver and kidney from the affected fetuses the disease-related enzyme activity of hexosaminidase A in TSD and β-galactosidase in Gm1-ganglactosidase) was less than 10% of control values. In liver, kidney, and brain extracts, cellulose-acetate gel electro-phoresis of the disease-specific enzyme revealed no bands of enzyme activity for hexosaminidase A in Tay-Sachs disease or for the relevant, β-galactosidase isoenzymes in Gm1-gangliosidosis.Speculation: The prenatal diagnosis of Tay-Sachs disease, Gm1-gangliosidosis, and other sphingolipidoses may be confirmed in saline-aborted fetal tissues. Since abortion by hysterotomy may jeopardize the possibility of future pregnancy, saline-induced abortion may be preferable. An intriguing observation of this study was the presence of a β-galactosidase isoenzyme in brain from the Gm1 fetus. This isoenzyme was clearly different from the disease-specific enzyme and was not present in fetal Gm1 liver or kidney or in postnatal type I Gm1 brain. This finding may indicate the presence of a tissue and age-specific β-galactosidase isoenzyme.