Mucolipidoses II and III: Heterozygote detection by quantitation of N-acetyl-β-D-glucosaminidase isozymes

Mucolipidoses (ML) II and III are inborn errors of lysosomal function characterized by intracellular deficiency of multiple lysosomal hydrolase activities, increased concentration of these enzymes in extracellular fluids, and the presence of cytoplasmic inclusion bodies. The primary molecular defects in these autosomal recessive disorders are unknown and identification of heterozygotes (hets) by intermediate levels of specific gene products is not possible. Since obligate hets for ML have increased amounts of thermostable N acetyl β D glucosaminidase (Hex) activity in plasma, we further characterized the plasma isozymes in order to evaluate their potential usefulness as markers for het identification. The %Hex I was determined in the plasma for homozygotes with ML II and III, their parents, relatives at risk for heterozygosity, and normal individuals. As shown below, ML II and III homozygotes and obligate hets had %Hex I values which distinguished them from normal individuals. Using this technique, 5 of 11 relatives at risk for heterozygosity for ML II has increased %Hex I values ranging from 28.6 to 35.8 whereas the remaining individuals had normal values (15.4 to 26.2%). In a ML III kindred, 23 relatives were studied; 10 were tentatively identified as carriers (32.7 to 41.4%) and 13 had normal values (15.2 to 26.9%). In the 3 kindreds examined, assignment of heterozygosity by this method was consistent with autosomal recessive transmission of ML genes.