Summary
The results of postmortem examinations in four I-cell disease (ICD) patients, 2 weeks, 8.5 months, 4 and 10 years of age, respectively, are compared and evaluated.
The most characteristic histological feature in ICD is the storage of membrane-bound vacuoles with fibrillo-granular contents in fibroblasts and of smaller inclusions with concentric ring-like profiles in endothelial cells. In older patients only, more heterogeneous cell inclusions with osmiophilic lamellar profiles may be found.
The morphological lesions in the central nervous system (CNS) are hardly significant.
Obvious abnormalities are present in the heart valves of even the very young patients, while alterations in the renal glomeruli are less severe in the long surviving patient. This difference may be viewed as histological confirmation of the proved genetic heterogeneity in ICD.
The paradox of cell type-specific morphological findings on the one hand and the generalized deficiency of N-acetylglucosamine-1-phosphotransferase representing the primordial enzyme deficiency in ICD on the other, is resolved by postulating, outside the mannose-6-phosphate recognition marker targeting system, the existence of alternative mechanisms for distribution and processing of lysosomal enzymes in cells other than fibroblasts or endothelial cells.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Aula P, Rapola J, Autio S, Raivio K Karjalainen O (1975) Prenatal diagnosis and fetal pathology of I-Cell disease (mucolipidosis type II). J Pediatr 87:221–226
Ghadially FN (1975) Ultrastructural pathology of the cell. Butterworths, London
Gilbert EF, Dawson G, Zu Rhein GM, Opitz JM, Spranger JW (1973) I-Cell disease, mucolipidosis II. Pathological, histochemical, ultrastructural and biochemical observations in four cases. Z Kinderheilkd 114:259–292
Hasilik A, Waheed A, von Figura K (1981) Enzymatic phosphorylation of lysosomal enzymes in the presence of UDP-N-acetylglucosamine; absence of the activity in I-Cell fibroblasts. Biochem Biophys Res Commun 98:761–767
Landing BH, Silverman FN, Craig JM, Jacobi MD, Lahey NE, Chadwick DL (1964) Familial neurovisceral lipidosis. An alysis of eight cases of a syndrome previously reported as “Hurler-Variant”, “pseudo-Hurler” and “Tay-Sachs disease with visceral involvement”. Am J Dis Child 108:503–522
Leroy JG (1983) The oligosaccharidoses (formerly mucolipidoses). In: Emery AE, Rimoin DL (eds) Principles and practice of medical genetics. Churchill Livingstone, Edinburgh, pp 1348–1365
Leroy JG, Martin JJ (1975) Mucolipidosis II (I-Cell disease): Present status of knowledge, In: Bergsma D (ed) Disorders of connective tissue. Stratton, New York, pp 283–293
Leroy JG, Spranger JW, Feingold M, Opitz JM, Crocker AC (1971) I-Cell disease: a clinical picture. J Pediatr 79:360–365
Leroy JG, Ho MW, MacBrinn MC, Zielke K, Jacob J, O'Brien BS (1972) I-Cell disease: biochemical studies. Pediatr Res 6:752–757
Libert J, Van Hoof F, Farriaux JP, Toussaint D (1977) Ocular findings in I-Cell disease (mucolipidosis type II). Am J Opthtalmol 83:617–628
Martin JJ, Ceuterick C (1983) Prenatal pathology in mucopolysaccharidoses; Comparison with postnatal cases. Clin Neuropathol 2:122–127
Martin JJ, Leroy JG, Farriaux JP, Fontaine G, Desnick RJ, Cabello A (1975) I-Cell disease (mucolipidosis II). A report on its pathology. Acta Neuropathol (Berl) 33:285–305
Martin JJ, Ceuterick C, Libert J (1979) Malattie metaboliche del sistema nervoso centrale del bambino. Approccio morfologica alla diagnosi. Prosp Pediatr 36:449–467
Nagashima K, Sakakibara K, Endo H, Konishi Y, Nakamura N, Suzuki Y, Abe T (1977) I-cell disease (mucolipidosis II). Pathological and biochemical studies of an autopsy case. Acta Pathol Jpn 27:251–264
Neufeld EF, McKusick VA (1983) Disorders of lysosomal enzyme synthesis and localisation: I-cell disease and pseudo-Hurler polydystrophy. In: Stanbury JB, Wyngaarden JB, Frederickson DS, Goldstein JS, Brown MS (eds) The metabolic basis of inherited disease, 5th edn. McGraw Hill, New York, pp 778–787
O'Brien JS, Stern MB, Landing BH, O'Brien JK, Donnell GN (1965) Generalized gangliosidosis: Another inborn error of ganglioside metabolism? Am J Dis Child 109:338–346
Reitman ML, Varki A, Kornfeld S (1981) Fibroblasts from patients with I-Cell disease and pseudo-Hurler polydystrophy are deficient in uridine 5′-diphosphate-N-acetylglucosamine: glycoprotein N-acetylglucosaminyl-phosphotrausferase activity. J Clin Invest 67:1574–1579
Scott CR, Lagunoff D, Trump BF (1967) Familial neurovisceral lipidosis. J Pediatr 71:357–366
Waheed A, Pohlmann JR, Hasilik A, von Figura K, Van Elsen A, Leroy JG (1982) Deficiency of UDP-N-acetylglucosamine: lysosomal enzyme N-acetylglucosamine-1-phosphotransferase in organs of I-Cell patients. Biochem Biophys Res Commun 105:1052–1058
Wiesmann UN, Herschkowitz N (1981) Mucolipidosis II and III. The clinical pictures and the pathogenetic mechanisms. In: Tettamanti G, Durand P, Di Donato S (eds) Perspectives in inherited metabolic diseases, vol. 4. Ermes, Milano, pp 347–451
Author information
Authors and Affiliations
Additional information
Supported by the FGWO (grant no. 3.0004.81) and the Baron C. Bracht Foundation
Rights and permissions
About this article
Cite this article
Martin, J.J., Leroy, J.G., van Eygen, M. et al. I-cell disease. Acta Neuropathol 64, 234–242 (1984). https://doi.org/10.1007/BF00688114
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00688114