{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T17:04:01Z","timestamp":1771002241719,"version":"3.50.1"},"reference-count":33,"publisher":"BMJ","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Archives of Disease in Childhood"],"published-print":{"date-parts":[[1973,10,1]]},"DOI":"10.1136\/adc.48.10.775","type":"journal-article","created":{"date-parts":[[2008,12,22]],"date-time":"2008-12-22T21:05:14Z","timestamp":1229979914000},"page":"775-785","source":"Crossref","is-referenced-by-count":79,"title":["Late onset GM2-gangliosidosis: Clinical, pathological, and biochemical studies on 8 patients"],"prefix":"10.1136","volume":"48","author":[{"given":"E. M.","family":"Brett","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. B.","family":"Ellis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Haas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. U.","family":"Ikonne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B. D.","family":"Lake","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. D.","family":"Patrick","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Stephens","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","reference":[{"key":"ref_1","article-title":"Bernheimer and Seitelberger","year":"1968","unstructured":"Bernheimer and Seitelberger (1968)"},{"key":"ref_2","author":"Volk","year":"1969","unstructured":"Volk et al. (1969), Klibansky et al. (1970), Schneck et al. (1970)","journal-title":"Klibansky et al. (1970), Schneck et al"},{"key":"ref_3","article-title":"Suzuki and Suzuki","author":"Suzuki","year":"1970","unstructured":"Suzuki et al. (1970), Suzuki and Suzuki (1970) Okada, Veath, and O'Brien (1970), Menkes et al. (1971)","journal-title":"Menkes et al; Okada, Veath, and O'Brien"},{"key":"ref_4","author":"Buxton","year":"1972","unstructured":"Buxton et al. (1972)"},{"key":"ref_5","article-title":"At necropsy the brain was superficially normal apart from the biopsy site. Biochemical studies on this patient have been reported","year":"1970","unstructured":"At necropsy the brain was superficially normal apart from the biopsy site. Biochemical studies on this patient have been reported (Young et al., 1970)."},{"key":"ref_6","article-title":"On admission in 1965, aged 4 years 3 months, she was retarded, speechless, and drooling, and had an exaggerated startle reaction to noise. Ophthalmoscopical examination was normal, but her vision was perhaps impaired. There was moderate hypotonia in all limbs and mild cerebellar ataxia was seen when she reached out for objects and walked. No other neurological signs were found. The spleen and liver were not enlarged","unstructured":"On admission in 1965, aged 4 years 3 months, she was retarded, speechless, and drooling, and had an exaggerated startle reaction to noise. Ophthalmoscopical examination was normal, but her vision was perhaps impaired. There was moderate hypotonia in all limbs and mild cerebellar ataxia was seen when she reached out for objects and walked. No other neurological signs were found. The spleen and liver were not enlarged."},{"key":"ref_7","article-title":"On admission, aged 5 years","volume-title":"8 months in; he was semicomatose. His head circumference was 45 cm. Cherry red spots of an unusual nature were present at the maculae; there was an irregular, poorly defined area of pallor surrounding the fovea. The fovea itself was not clearly demarcated and was not circular in outline (Fig. 1). All limbs were spastic; tendon reflexes were exaggerated and plantar responses extensor. Neither spleen nor liver was enlarged","year":"1970","unstructured":"On admission, aged 5 years 8 months in 1970, he was semicomatose. His head circumference was 45 cm. Cherry red spots of an unusual nature were present at the maculae; there was an irregular, poorly defined area of pallor surrounding the fovea. The fovea itself was not clearly demarcated and was not circular in outline (Fig. 1). All limbs were spastic; tendon reflexes were exaggerated and plantar responses extensor. Neither spleen nor liver was enlarged."},{"key":"ref_8","article-title":"Case 5. The younger sister of Case 4 was born in 1971 and was normal until the age of 13 months when she became unsteady in walking and fell frequently. At 14 months she became abnormally sensitive to sound. Examination at 16 months showed an alert, intelligent toddler who would jump and give a cry in response to any sudden noise. Ophthalmoscopy suggested bilateral cherry red spots. She walked unsteadily with her legs internally rotated. Tone and power in the limbs were normal, but tendon reflexes in the legs were exaggerated. Plantar responses were flexor. No definite deterioration has occurred between the ages of 16 and 21 months. Investigations so far have been limited to enzyme studies on white blood cells (Table II)","unstructured":"Case 5. The younger sister of Case 4 was born in 1971 and was normal until the age of 13 months when she became unsteady in walking and fell frequently. At 14 months she became abnormally sensitive to sound. Examination at 16 months showed an alert, intelligent toddler who would jump and give a cry in response to any sudden noise. Ophthalmoscopy suggested bilateral cherry red spots. She walked unsteadily with her legs internally rotated. Tone and power in the limbs were normal, but tendon reflexes in the legs were exaggerated. Plantar responses were flexor. No definite deterioration has occurred between the ages of 16 and 21 months. Investigations so far have been limited to enzyme studies on white blood cells (Table II)."},{"key":"ref_9","article-title":"On examination in 1969, aged 10 years, he was a demented boy with frequent myoclonic jerks of the hands. Photophobia made ophthalmological examination difficult, but mild bilateral optic atrophy and a cherry red spot on the right were seen. There was spasticity in all limbs, with hands tightly clenched and feet in equinus with shortened Achilles tendons. The tendon reflexes were normal, plantar responses flexor, and abdominal reflexes absent. The spleen and liver were not palpable","unstructured":"On examination in 1969, aged 10 years, he was a demented boy with frequent myoclonic jerks of the hands. Photophobia made ophthalmological examination difficult, but mild bilateral optic atrophy and a cherry red spot on the right were seen. There was spasticity in all limbs, with hands tightly clenched and feet in equinus with shortened Achilles tendons. The tendon reflexes were normal, plantar responses flexor, and abdominal reflexes absent. The spleen and liver were not palpable."},{"key":"ref_10","article-title":"Deterioration has continued and now, at the age of 13k, he is completely demented, wasted, and immobile with a continuous tremulous activity in the lower half of his mask-like face","year":"1971","unstructured":"Deterioration has continued and now, at the age of 13k, he is completely demented, wasted, and immobile with a continuous tremulous activity in the lower half of his mask-like face. Cumings has referred to this patient on two occasions (1968, 1971)."},{"key":"ref_11","first-page":"163","article-title":"Ober das Verhalten der Ganglioside im Gehirn bei 2 FAllern von spatinfantiler amaurotischer Idiotie","volume":"80","author":"Bernheimer, H.; Seitelberger, F.","year":"1968","unstructured":"Bernheimer, H., and Seitelberger, F. (1968). Ober das Verhalten der Ganglioside im Gehirn bei 2 FAllern von spatinfantiler amaurotischer Idiotie. WienerKlinische Wochenschrift, 80, 163.","journal-title":"WienerKlinische Wochenschrift"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1002\/bjs.18005022507","article-title":"The rectal approach to neuropathology","volume":"50","author":"Bodian, M.; Lake, B.D.","year":"1963","unstructured":"Bodian, M., and Lake, B. D. (1963). The rectal approach to neuropathology. British Journal of Surgery, 50, 702.","journal-title":"British Journal of Surgery"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1136\/jnnp.35.5.685","article-title":"A case of GM2 gangliosidosis of late onset","volume":"35","author":"Buxton, P.; Cumings, J.N.; Ellis, R.B.; Lake, B.D.; Mair, W.G.P.; Roberts, J.R.; Young, E.P.","year":"1972","unstructured":"Buxton, P., Cumings, J. N., Ellis, R. B., Lake, B. D., Mair, W. G. P., Roberts, J. R., and Young, E. P. (1972). A case of GM2 gangliosidosis of late onset. Journal of Neurology, Neurosurgery and Psychiatry, 35, 685.","journal-title":"Journal of Neurology, Neurosurgery and Psychiatry"},{"key":"ref_14","first-page":"268","article-title":"Genetically determined neurological diseases of children. In Biochemical Aspects of Neurological Disorders, 3rd series","author":"Cumings, J.N.","year":"1968","unstructured":"Cumings, J. N. (1968). Genetically determined neurological diseases of children. In Biochemical Aspects of Neurological Disorders, 3rd series, p. 268. Ed. by J. N. Cumings and M. Kremer. Blackwell, Oxford."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1177\/003591577106400335","article-title":"Inborn errors of metabolism in neurology (Wilson's disease, Refsum's disease, and lipidoses)","volume":"64","author":"Cumings, J.N.","year":"1971","unstructured":"Cumings, J. N. (1971). Inborn errors of metabolism in neurology (Wilson's disease, Refsum's disease, and lipidoses). Proceedings of the Royal Society of Medicine, 64, 313.","journal-title":"Proceedings of the Royal Society of Medicine"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1016\/S0140-6736(69)92520-3","article-title":"N-acetylhexosaminidase activities in TaySachs disease","volume":"2","author":"Hultberg, B.","year":"1969","unstructured":"Hultberg, B. (1969). N-acetylhexosaminidase activities in TaySachs disease. (Letter to Editor.) Lancet, 2, 1195.","journal-title":"(Letter to Editor.) Lancet"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1111\/j.1471-4159.1970.tb02220.x","article-title":"Cerebral lipids in a case of systemic GM2gangliosidosis of a late infantile type","volume":"17","author":"Klibansky, C.; Saifer, A.; Feldman, N.I.; Schneck, L.; Volk, B.W.","year":"1970","unstructured":"Klibansky, C., Saifer, A., Feldman, N. I., Schneck, L., and Volk, B. W. (1970). Cerebral lipids in a case of systemic GM2gangliosidosis of a late infantile type. Journal of Neurochemistry, 17, 339.","journal-title":"Journal of Neurochemistry"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1001\/archneur.1971.00490010024003","article-title":"Juvenile GM2 gangliosidosis. Biochemical and ultrastructural studies on a new variant of Tay-Sachs disease","volume":"25","author":"Menkes, J.H.; O'Brien, J.S.; Okada, S.; Grippo, J.; Andrews, J.M.; Cancilla, P.A.","year":"1971","unstructured":"Menkes, J. H., O'Brien, J. S., Okada, S., Grippo, J., Andrews, J. M., and Cancilla, P. A. (1971). Juvenile GM2 gangliosidosis. Biochemical and ultrastructural studies on a new variant of Tay-Sachs disease. Archives of Neurology, 25, 14.","journal-title":"Archives of Neurology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1093\/brain\/96.1.97","article-title":"A neurovisceral storage disease with vertical supranuclear ophthalmoplegia, and its relationship to Niemann-Pick disease","volume":"96","author":"Neville, B.G.R.; Lake, B.D.; Stephens, R.; Sanders, M.D.","year":"1973","unstructured":"Neville, B. G. R., Lake, B. D., Stephens, R., and Sanders, M. D. (1973). A neurovisceral storage disease with vertical supranuclear ophthalmoplegia, and its relationship to Niemann-Pick disease. Brain, 96, 97.","journal-title":"Brain"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1056\/NEJM197007022830104","article-title":"Tay-Sachs disease. Detection of heterozygotes and homozygotes by serum hexosaminidase assay","volume":"283","author":"O'Brien, J.S.; Okada, S.; Chen, A.; Fillerup, D.L.","year":"1970","unstructured":"O'Brien, J. S., Okada, S., Chen, A., and Fillerup, D. L. (1970). Tay-Sachs disease. Detection of heterozygotes and homozygotes by serum hexosaminidase assay. New England Journal of Medicine, 283, 15.","journal-title":"New England Journal of Medicine"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1126\/science.165.3894.698","article-title":"Tay-Sachs disease: generalized absence of a beta-D-N-acetylhexosaminidase component","volume":"165","author":"Okada, S.; O'Brien, J.S.","year":"1969","unstructured":"Okada, S., and O'Brien, J. S. (1969). Tay-Sachs disease: generalized absence of a beta-D-N-acetylhexosaminidase component. Science, 165, 698.","journal-title":"Science"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1016\/S0022-3476(70)80096-8","article-title":"Juvenile GM2 gangliosidosis: partial deficiency of hexosaminidase A","volume":"77","author":"Okada, S.; Veath, M.L.; O'Brien, J.S.","year":"1970","unstructured":"Okada, S., Veath, M. L., and O'Brien, J. S. (1970). Juvenile GM2 gangliosidosis: partial deficiency of hexosaminidase A. Journal of Pediatrics, 77, 1063.","journal-title":"Journal of Pediatrics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1042\/bj1020533","article-title":"Rat-urine glycosidases and kidney damage","volume":"102","author":"Robinson, D.; Price, R.G.; Dance, N.","year":"1967","unstructured":"Robinson, D., Price, R. G., and Dance, N. (1967). Rat-urine glycosidases and kidney damage. Biochemical Journal, 102, 533.","journal-title":"Biochemical Journal"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1042\/bj1070321","article-title":"N-acetyl-(3-glucosaminidases in human spleen","volume":"107","author":"Robinson, D.; Stirling, J.L.","year":"1968","unstructured":"Robinson, D., and Stirling, J. L. (1968). N-acetyl-(3-glucosaminidases in human spleen. 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Pathologia Europaea, 3, 278.","journal-title":"Pathologia Europaea"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"997","DOI":"10.3181\/00379727-133-34613","article-title":"Hexosaminidase activities in a case of systemic GM2gangliosidosis of late infantile type","volume":"133","author":"Schneck, L.; Friedland, J.; Pourfar, M.; Saifer, A.; Volk, B.W.","year":"1970","unstructured":"Schneck, L., Friedland, J., Pourfar, M., Saifer, A., and Volk, B. W. (1970). Hexosaminidase activities in a case of systemic GM2gangliosidosis of late infantile type. Proceedings of the Society for Experimental Biology and Medicine, 133, 997.","journal-title":"Proceedings of the Society for Experimental Biology and Medicine"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S0022-2275(20)38922-7","article-title":"Brain ceramide hexosides in Tay-Sachs disease and GM1-gangliosidosis","volume":"8","author":"Suzuki, K.; Chen, G.C.","year":"1967","unstructured":"Suzuki, K., and Chen, G. C. (1967). Brain ceramide hexosides in Tay-Sachs disease and GM1-gangliosidosis. Journal of Lipid Research, 8, 105.","journal-title":"Journal of Lipid Research"},{"key":"ref_29","author":"Suzuki, K.; Suzuki, K.; Rapin, I.; Suzuki, Y.; Ishii, N.","year":"1970","unstructured":"Suzuki, K., Suzuki, K., Rapin, I., Suzuki, Y., and Ishii, N. (1970)."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1212\/WNL.20.9.848","article-title":"Partial deficiency of hexosaminidase component A in juvenile GM2-gangliosidosis","volume":"20","author":"Suzuki, Y.; Suzuki, K.","year":"1970","unstructured":"Suzuki, Y., and Suzuki, K. (1970). Partial deficiency of hexosaminidase component A in juvenile GM2-gangliosidosis. Neurology, 20, 848.","journal-title":"Neurology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/0006-291X(62)90030-X","article-title":"The chemical structure of normal human brain and Tay-Sachs gangliosides","volume":"9","author":"Svennerholm, L.","year":"1962","unstructured":"Svennerholm, L. (1962). The chemical structure of normal human brain and Tay-Sachs gangliosides. Biochemical and Biophysical Research Communications, 9, 436.","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"ref_32","first-page":"393","article-title":"G5-ganglioside variant of systemic late infantile lipidosis; generalized gangliosidosis","volume":"87","author":"Volk, B.W.; Adachi, M.; Schneck, L.; Saifer, A.; Kleinberg, W.","year":"1969","unstructured":"Volk, B. W., Adachi, M., Schneck, L., Saifer, A., and Kleinberg, W. (1969). G5-ganglioside variant of systemic late infantile lipidosis; generalized gangliosidosis. Archives of Pathology, 87, 393.","journal-title":"Archives of Pathology"},{"issue":"1","key":"ref_33","article-title":"Tay-Sachs disease and related disorders: fractionation of brain N-acetyl-, l-hexosaminidase on DEAE-cellulose","volume":"9","author":"Young, E.P.; Ellis, R.B.; Lake, B.D.; Patrick, A.D.","year":"1970","unstructured":"Young, E. P., Ellis, R. B., Lake, B. D., and Patrick, A. D. (1970). 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