Beginning with an infant screened for Sandhoff disease, Alexander et al. (1984) found 5 healthy persons in 3 generations of a Lebanese family with high levels of lysosomal enzymes in the plasma comparable to those found in mucolipidoses ... Beginning with an infant screened for Sandhoff disease, Alexander et al. (1984) found 5 healthy persons in 3 generations of a Lebanese family with high levels of lysosomal enzymes in the plasma comparable to those found in mucolipidoses II and III (252500, 252600) homozygotes. The same enzymes were within normal limits in other extracellular fluids; in ML II/III, they are elevated in urine and cerebrospinal fluid. As with ML II/III patients, levels of acid phosphatase, alkaline phosphatase and beta-glucuronidase were normal. Two alternative possibilities were considered: (1) a defect in the phosphodiesterase that normally uncovers the mannose 6-phosphate marker, or (2) a defect in the mannose 6-phosphate receptor. One might expect that an enzyme defect would not be expressed in the heterozygote. On the other hand, defects in the LDL receptor (606945) are so expressed. Mutant Chinese hamster ovary cells with altered mannose 6-phosphate receptors were studied by Robbins and Myerowitz (1981). Although the kindred studied was consanguineous, the pattern of inheritance appeared to be autosomal dominant; one instance of male-to-male transmission was noted. Alexander et al. (1986) showed that mannose 6-phosphate receptors in the fibroblasts from a member of this family were functioning normally but the cells had only half-normal levels of phosphodiester glycosidase activity. Pinocytosis into Sandhoff disease fibroblasts of beta-hexosaminidase B secreted by the fibroblasts of this person was 18% of control. Treatment of the abnormal Hex-B with exogenous placental phosphodiester glycosidase (607985) increased its binding to mannose 6-phosphate receptors 3-fold. Secretion rates of 7 lysosomal enzymes from the subject's fibroblasts were, on average, twice as great as rates measured for 2 I-cell disease heterozygote fibroblast lines. Alexander et al. (1986) suggested that an individual homozygous for this enzyme deficiency would develop I-cell disease.