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Heterozygosity for phosphodiester glycosidase deficiency: a novel human mutation of lysosomal enzyme processing

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Summary

We have carried out studies on the fibroblasts of III-3, a clinically normal Lebanese individual previously reported to have abnormally high plasma lysosomal enzyme levels. Mannose-6-phosphate (man-6-P) receptors in III-3 fibroblasts were found to be functioning normally, but the cells had only half normal levels of phosphodiester glycosidase activity. Pinocytosis of III-3 fibroblast secreted β-hexosaminidase B (hex B) into Sandhoff disease fibroblasts was 18% of control, and the apparent KD for binding of III-3 hex B to man-6-P receptors was 3.7x10-9 M compared to 1.25x10-9 M for control enzyme. Hex B secreted by III-3 fibroblasts included an enzyme pool less electro-negative than controi enzyme which had a very low affinity for man-6-P receptors and which did not bind to DEAE-Sephadex. Treatment of this abnormal hex B with exogenous placental phosphodiester glycosidase increased its binding to man-6-P receptors three-fold. Secretion rates of seven lysosomal enzymes from III-3 fibroblasts were, on average, twice as great as rates measured for two I-cell disease heterozygote fibroblast lines. The results suggest that III-3 fibroblasts are heterozygous for phosphodiester glycosidase deficiency. The possibility that an individual homozygous for this enzyme deficiency would develop I-cell disease is discussed.

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Authors and Affiliations

  1. National Unit of Human Genetics, Department of Pediatrics, American University of Beirut Medical Center, Beirut, Lebanon

    D. Alexander, Marlene Deeb & F. Talj

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  1. D. Alexander
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  2. Marlene Deeb
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  3. F. Talj
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Alexander, D., Deeb, M. & Talj, F. Heterozygosity for phosphodiester glycosidase deficiency: a novel human mutation of lysosomal enzyme processing. Hum Genet 73, 53–59 (1986). https://doi.org/10.1007/BF00292664

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  • DOI: https://doi.org/10.1007/BF00292664

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