Summary
Clinical, neurochemical and neuropathological findings on a case of late-infantile Gaucher disease with oculomotor apraxia, progressive myoclonus and prominent bulbar signs are reported. There was a marked increase in glucosylceramide in cerebral cortex and cerebellum; the increase was more in the range of that seen in the Norrbottnian type III than in type II Gaucher disease. Cerebral cortical changes were characterized by a band-like intraparenchymal accumulation of Gaucher cells in lamina IV with an accompanying astrogliosis. In the cerebellum, a focal severe loss of granule cells and a global loss of dentate nucleus neurons was recorded. Milder changes were seen in thalamus and brain stem where perivascular accumulation of Gaucher cells was present in all regions. The cerebral cortical changes resembled those seen in type II Gaucher disease and was much more marked than in the Norrbottnian type III, whereas the changes in the dentate nucleus were more severe than in both type II and type III. The phenotypic variability with different patterns of clinical symptoms and neuropathological changes in neuronopathic Gaucher disease is discussed.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Conradi NG, Sourander P, Nilsson O, Svennerholm L, Eriksson A (1984) Neuropathology of the Norrbottnian type of Gaucher disease. Acta Neuropathol (Berl) 65:99–104
Dreborg S, Eriksson A, Hagberg B (1980) Gaucher disease —Norrbottnian type. I. General clinical description. Eur J Pediatr 133:107–118
Eriksson A (1986) Gaucher disease — Norrbottnian type (III). Neuropediatric and neurobiological aspects of clinical patterns and treatment. Acta Paediatr Scand [Suppl] 326:1–41
Fabbro D, Desnick RJ, Grabowski GA (1987) Gaucher disease: genetic hetogeneity within and among the subtypes detected by immunoblotting. Am J Hum Genet 40:15–31
Grover WD, Tucker SH, Wenger DA (1978) Clinical variation in two related children with neuronopathic Gaucher disease. Ann Neurol 3:281–283
Haltia M, Kristensson K, Sourander P (1968) Neuropathological studies in three Scandinavian cases of progressive myoclonus epilepsy. Acta Neurol Scand 45:63–77
Herrlin KM, Hillborg PO (1962) Neurological signs in a juvenile form of Gaucher's disease. Acta Paediatr Scand 51:137–154
Hillborg PO, Svennerholm L (1960) Blood levels of cerebrosides in Gaucher's disease. Acta Paediatr Scand 49:707–710
Kaye EM, Ullman MD, Wilson ER, Barranger JA (1986) Type 2 and type 3 Gaucher's disease: a morphological and biochemical study. Ann Neurol 20:223–230
King JO (1975) Progressive myoclonus epilepsy due to Gaucher's disease in an adult. J Neurol Neurosurg Psychiatry 38:849–854
Kyllerman M, Conradi N, Månsson J-E, Percy AK, Svennerholm L (1990) Partial splenectomy in a child with Gaucher type III disease. Acta Paediatr Scand 79:448–453
Miller JD, McCluer R, Kanfer JW (1973) Gaucher's disease. neurological disorder in adult siblings. Ann Intern Med 78:883–887
Nilsson O, Svennerholm (1982) Accumulation of glucosylceramide and glucosylsphingosine (psychosine) in cerebrum and cerebellum in infantile and juvenile Gaucher disease. J Neurochem 39:709–718
Nilsson O, Håkansson G, Dreborg S, Groth CG, Svennerholm L (1982) Increased cerebroside concentration in plasma and erythrocytes in Gaucher disease: significant differences between type I and type III. Clin Genet 22:274–279
Nishimura RN, Barranger JA (1980) Neurologic complication of Gaucher's disease type III. Arch Neurol 37:92–93
Rapin I (1986) Myoclonus in neuronal storage and Lafora diseases. Adv Neurol 43:67–68
Seitelberger F (1964) Über die Gehirnbeteiligung bei der Gaucherschen Krankheit im Kindesalter. Arch Psychiatr. Z Neurol 206:419–440
Svennerholm L, Fredman P (1980) A procedure for the quantitative isolation of brain gangliosides. Biochim Biophys Acta 817:97–109
Svennerholm L, Vanier MT, Månsson J-E (1980) Krabbe disease: a galactosylsphingosine (psychosine) lipidosis. J Lipid Res 21:53–64
Svennerholm L, Håkansson G, Månsson J-E, Nilsson O (1982) Chemical differentiation of the Gaucher subtypes. In: Desnick RJ, Gatt S, Grabowski GA (eds) Gaucher disease: a century of delineation and research. Alan R Liss, pp 231–252, New York
Svennerholm L, Månsson J-E, Rosengren B (1986) Cerebroside-β-glucosidase activity in Gaucher brain. Clin Genet 30:131–135
Svennerholm L, Fredman P, Jungbjer B, Månsson J-E, Boström K, Hagberg B, Norén L, Santavouri P (1987) Large alteration in ganglioside and neutral glycosphingolipid patterns in brains from cases with infantile neuronal ceroid lipofuscinosis/polyunsaturated fatty acid lipidosis. J Neurochem 49:1772–1783
Theophilus B, Latham T, Grabowski GA, Smith FI (1989) Gaucher disease: molecular heterogeneity and phenotypegenotype correlations. Am J Hum Genet 45:212–225
Tripp JH, Lake BD, Young E, Ngu J, Brett EM (1977) Juvenile Gaucher's disease with horizontal gaze palsy in three siblings. J Neurol Neurosurg Psychiatry 40:470–478
Tsuji S, Choudary PV, Martin BM, Stubblefield BK, Mayor JA, Barranger JA, Ginns EI (1987) A mutation in the human glucocerebroside gene in neuronopathic Gaucher's disease. N Engl J Med 316:570–575
Winkelman MD, Banker BQ, Victor M, Moser HW (1983) Non-infantile neuronopathic Gaucher's disease: a clinicopathologic study. Neurology 33:994–1008
Author information
Authors and Affiliations
Additional information
Supported by grants from the Swedish Medical Research Council (project nos. 00627 and 07121). AKP was at the time of the study a visiting Professor from Baylor College, Houston, TX
Rights and permissions
About this article
Cite this article
Conradi, N., Kyllerman, M., Månsson, J.E. et al. Late-infantile Gaucher disease in a child with myoclonus and bulbar signs: neuropathological and neurochemical findings. Acta Neuropathol 82, 152–157 (1991). https://doi.org/10.1007/BF00293959
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00293959