| OCR Text |
Show [ournal of Clinical Neliro-of,hUUltll/oloSY 7(1): 40-44, 1987 Sialidosis (Neuraminidase Deficiency) Types I and II: Neuro-ophthalmic Manifestations J. Stanwood Till, M.D., E. S. Roach, M.D., and Barbara K. Burton, M.D. © 1987 Raven Press, New York The clinical details and ophthalmologic findings of two siblings with neuraminidase deficiency (sialidosis) are presented. One patient is best classified as having sialidosis type 1, while the younger sibling has features of type II. Both exhibited classic cherry-red macular abnormalities, and the patient who would permit complete ophthalmologic examination had both corneal and lenticular opacities. Markedly reduced neuraminidase activity was demonstrated in both patients. These two patients, and 48 others from the literature, were reviewed to determine the frequency of various ophthalmologic abnormalities with sialidosis. Macular cherry-red spots were present in all adequately described type I patients and all but three patients with type II disease. Visual field defects, diminished acuity, and optic atrophy, though less well documented, occurred in the majority of both type I and type II patients. Lenticular lesions were present in all but two of the 18 patients with detailed ocular examination, whereas corneal opacities were found more often in type II than type I disease. Key Words: Sialidosis-Neuraminidose deficiencyMacular abnormality-Lenticular lesions-Myoclonus syndrome. From the Departments of Ophthalmology (l.S.T.), Neurology (E.S.R.). and Pediatrics (B.K.B.), Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina. Dr. Till's present address is The Lewis-Gale Clinic, Salem, Virginia. Address correspondence and reprint requests to Dr. E. S. Roach, Department of Neurology, Bowman Gray School of Medicine. Wake Forest University, Winston-Salem, NC 27103, Neuraminidase deficiency, or sialidosis, is an autosomal recessive deficiency of the enzyme alpha-N-acetylneuraminic acid hydrolase (1). The term sialidosis was first suggested by Durand et aI. (2) for patients with marked accumulation of sialic acid glycoconjugates in the urine and body tissues. On the basis of age of onset and other clinical features, the disorder has been divided into subtypes I and II (1). Type I was previously referred to as the cherry-red spot-myoclonus syndrome. Type II sialidosis has been further subdivided into juvenile and infantile categories. Type I sialidosis often presents with myoclonus in adolescence and is rarely associated with mental retardation, dysmorphic features, visceromegaly, or hearing loss. Juvenile type II sialidosis tends to have a somewhat earlier age of onset and is more frequently associated with mental retardation and dysmorphic features, whereas the infantile form of type II usually begins during the first year and is invariably associated with visceromegaly, hearing loss, and dysmorphic changes. Lowden and O'Brien (1) summarized the 37 known and suspected cases of sialidosis through 1979, including 18 patients with type I and 19 patients with type II disease. We report two additional patients, one best classified as haVing type I and the other as having features of juvenile type II disease. Using our two patients and 48 others from the medical literature, we attempt to determine the frequency of various ophthalmologic abnormalities in this disorder. CASE REPORTS Patient 1 A 16-year-old white girl was evaluated for a 2year history of progressive ataxia. Her gait was so NEURO-OPHTHALMIC MANIFESTATIONS OF SIALIDOSIS 41 .- . .- -... .- A12~year-oldboy, a sibling of patient -I,had a history of poor intellectual development dating to three periCeritral scotomata in each eye, but there was some difficulty in testingin that the patient was- slow to respond.-On slit lamp examination, there were two distinct anterior stromal opacities in the right eye, one -.2mm and the other 1 mm in diameter (Fig. 1). N()similaropacities'were found in-the left eye:-Theanteriorchamberswere deep and dear, and the irides were normal. Both lenses had fine opacities in a lamellar distribution. The vitreous was normaL Tonometry by applanation showed intraocular pressures of 14 mmHg in the right eye and 17 mmHg inthe left eye. Both ,maculae had thetypical cherry-red spot (Fig. 2). The retinal vasculature was normal, and l1oabnormalities of the peripheral retina were evident. The discs had large physiologic cups. The results of laboratory studies, including computerized cranial tomography, brainstem and somatosensory evoked responses, electroencephalo- 'gram,serum chemistry, peripheral cell count, rheumatoid faCtor; _and sedimentation rate, were normal. The chest radiograph --revealed mild scoIiosisbuf was otherwise normal. Visual evoked responses were minimally-abnormal because of bilaterally delayed conduction times. Enzyme studies on cultured skin fibroblasts revealed 3.3% of normal neuraminidase activity with normal activity of other lysosomal hydrolases. unsteady that she frequel1tlyfelI,andduring the previous few months she had also noticed trouble , holding onto objects: We were unable todocu-__ ment intellectual deterioration, since the patient was poorly cooperative with psychological studies. Her grades in school had dropped substantially .sirice _the time of herdiagnosis, perhaps owing inpartto her frequent absences from school rather than to intellectual deterioration. She had no family history of gait disturbance, but a-younger brother (patient 2) had a'long history of nonpro-gressivemental retardation. - - The results of general physical examination and her-mental status were normaL She had slightly decreased strength in the hands and increased muscle tone inthe legs. The deep tendon reflexes were hyperactive, especially in the legs,where ankle clonus waspresenLA restingtremor,'which worsened with movement, was noted. The gait was wide-based and markedly ataxic; and she could •not tandem walk. Her cranial nerves and sensation were normal. Ophthalmologic examination showed -- heibest corrected visual acuity to be 20/30 in each eye with -1.50~3.00 x 180 in ,the ,right eye and-4.00 -: 2.50 x 180 in the left eye. Her color vision'was poor: orily two of 18 Ishihara jsochromaticplates were correctly named with either eye, The pupils were 3 mmineach.eyeand.normallyreactive with no afferent defect. The lids were normal. The eye movements were normal, although an end-point 'nystagmus was present on horizontal gaze. Visual fields with _the Goldman perimeter demonstrated FIG. 1. -Cor~MI'o~acitie~ (arrow) of~aient1. . " ,/ '.,',," , CiiIlN~uro-oplrt;lQh~ol. V~1. i,No_ 1, 1987 NEURO-OPHTHALMIC MANIFESTATIONS OF SIALIOOSIS 43 only rarely do they have mental retardation, hearing loss, dysmorphic features, or visceromegaly. Patients with type II juvenile sialidosis typically have dysmorphic features but not visceromegaly, whereas children with infantile type II disease have hearing loss, dysmorphic features, visceromegaly, and the onset of symptoms during the first year of life. Our two patients illustrate the difficulty of a classification scheme based solely on clinical features: although they were siblings, each had features of a separate clinical subtype of neuraminidase deficiency. An adequate explanation for these dissimilar presentations will probably depend on additional delineation of the genetic and biochemical basis for the subtypes. Many of the reported patients with neuraminidase deficiency have had incomplete documentation of their ophthalmologic findings, including our second patient, who was retarded and would not cooperate with slit lamp examination. The frequency of various ophthalmologic findings in the adequately documented patients is summarized in Table 2. Regardless of the subtype, most affected patients have cherry-red macular lesions. The three patients with documented absence of these lesions were type II patients at the extremes of age: one patient was 48 years old (5) and two were 8 months (6) and 15 months (7) of age. There have been reports of cherry-red spots fading or even disappearing over time in patients with Tay-Sachs disease (3) and in those with both type I (4) and type II juvenile sialidosis (8). Progressive deterioration of vision is commonly noted, but the visual acuity may be normal or only mildly diminished, as in our first patient. Corneal opacities have been reported with all clinical types of neuraminidase deficiency, though they are more commonly seen in type II than type I disease. The unilateral corneal opacity in our first patient is somewhat surprising, though we suspect that with time the lesions will be evident bilaterally. Fine punctate lenticular opacities have been de- TABLE 2. Ophthalmologic findings in sialidosis· Type II Type I Juvenile Infantile Decreased acuity 15/19 11/11 NR Loss of color vision 4/4 2/2 NR Lenticular lesions 9/10 5/6 2/2 Cherry-red macula 25/25 13/14 3/5 Visual field defect 7/8 1/1 NR Optic atrophy 7/10 3/3 NR Corneal lesions 3/16 11/14 2/4 NR, not reported. • Information from references 1, 2, 4, 5-9, 12-38. scribed in several patients, and in our first patient, these lesions were found in a lamellar distribution in the area of the adult nucleus. Other authors have reported opacities in the anterior and posterior subcapsular spaces, or white flake-like lesions in the adult lens reminiscent of those seen with myotonic dystrophy (9). Neuraminic acid-containing macromolecules are an integral component of the normal lens (10,11), and it is not surprising that these opacities are so common in sialidosis. Optic atrophy may result from the accumulation of metabolic products in the ganglion cells, leading to axonal atrophy. Visual field defects have included paracentral scotomata (9,12,13), centrocecal defects (14), and enlargement of the blind spot (15). While most hereditary neurologic disorders of children are not currently treatable, the early diagnosis of these disorders is important for establishing the prognosis and for proper genetic counseling. Recognition of the typical ocular manifestations of neuraminidase deficiency by the ophthalmologist may help to establish the diagnosis of this recently described disorder. Acknowledgment: We thank Mr. Marshall Tyler for the corneal and retinal photographs. REFERENCES 1. Lowden JA, O'Brien J. Sialidosis: a review of human neuraminidase deficiency. Am JHum Genet 1979;31:1-18. 2. Durand P, Gatti R, Cavalieri 5, et al. Sialidosis (mucolipidoses I). Helv Paediatr Acta 1977;32:391-400. 3. Kivlin JD, Sanborn GE, Myers GG. The cherry-red spot in Tay-Sachs and other storage diseases. Ann Neural 1985;17: 356-60. 4. O'Brien JS. The cherry red spot-myoclonus syndrome: a newly recognized inherited lysosomal storage disease due to acid neuraminidase deficiency. Clin Genet 1978;14:55-60. 5. Miyatake T, Atsumi T, Obayashi T, et al. Adult type neuronal storage disease with neuraminidase deficiency. AmI Neural 1979;6:232-44. 6. Kelly TE, Graetz G. Isolated acid neuraminidase deficiency. Am J Med Genet 1977;1:31-46. 7. Aylsworth AS, Thomas GH, Hood JL, Malouf N, Libert J. A severe infantile sialidosis: clinical, biochemical and microscopic features. JPediatr 1980;96:662-8. 8. Thomas GH, Goldberg MF, Miller CS, Reynolds LW. Neuraminidase deficiency in the original patient with the Goldberg syndrome. Clin Genet 1979;16:323-30. 9. Thomas PK, Abrams JD, Swallow 0, Stewart G. Sialidosis type I: cherry red spot-myoclonus syndrome with sialidase deficiency and altered electrophoretic mobilities of some enzymes known to be glycoproteins. JNeural Neurosurg Psychiatry 1979;42:873-80. 10. Dische Z. Glycoproteins of the lens. Invest Ophtlwlmal 1965;4:174-80. 11. Hadad H, Becker B. Distribution of sialic acids in the human eye. Arch OphthalmoI1961;65:563-4. 12. Sogg RL, Steinman L, Rathjen B, Tharp BR, O'Brien JS. Cherry-red spot-myoclonus syndrome. Ophthalmology 1979;86:1861-73. . 13. Steinman L, Tharp BR, Dorfman L}, et al. Peripheral neu- J Clin Neuro-oplzthalmol. Vol. 7. No.1, 1987 44 J. S. TILL ET AI. ropathy in the cherry-red spot-myoclonus syndrome. Ann Neural 1979;7:450-6. 14. Tittarelli R, Giagheddu M, Spadetta V. Typicalophthalmoscopic picture of "cherry red spot" in an adult with the myoclonic syndrome. Br JOphthamaI1966;50:414-20. 15. Thomas GH, Tipton RE, Ch'ien LT, Reynolds LW, Miller CS. Sialidase (alpha-N-acetyl neuraminidase) deficiency: the enzyme defect in an adult with macular cherry-red spots and myoclonus without dementia. Clin Genet 1978; 13:369-79. 16. Anderson B, Margolis G, Lynn WS. Ocular lesions related to disturbances in fat metabolism. Am JOphthalmaI1958;45: 23-41. 17. Den Tandt WR, Leroy JG. Deficiency of neuraminidase in the sialidoses and the mucolipidoses. Hum Genet 1980;53: 383-9. 18. Federico A, Cecio A, Battini GA, Michalski Je, Strecker G, Guazzi Gc. Macular cherry-red spot and myoclonus syndrome. JNeural Sci 1980;48:157-69. 19. Franceschetti S, Uziel G, Di Donato S, Caimi L, Avanzini G. Cherry-red spot myoclonus syndrome and alpha-neuraminidase deficiency: neurological, pharmacological and biochemical study in an adult. JNeural Neurasurg Psychiatry 1980;43:934-40. 20. Goldstein ML, Kolodny EH, Gascon GG, Gilles FH. Macular cherry-red spot, myoclonic epilepsy, and neurovisceral storage in a 17-year old girl. Trans Am Neural Assac 1974;99:110-2. 21. Hambert 0, Petersen I. Clinical, electroencephalographical and neuropharmacological studies in syndromes of progressive myoclonus epilepsy. Acta Neural Scand 1970;46: 149-86. 22. Hong VN, Beauregard G, Potier M, et al. Studies on the sialidoses. Biachim Biaphys Acta 1980;616:259-70. 23. Hootgeveen AT, Verheijen FW, d'Azzo A, Galjaard H. Genetic heterogeneity in human neuraminidase deficiency. Nature 1980;285:500-1. 24. Itoyama Y, Goto F, Kuroiwa Y, Takeichi M, Kawabuchi M, Tanaka Y. Familial juvenile neuronal storage disease. Arch Neural 1978;35:792-800. 25. Justice PM, Wenger DA, Naidu S, Rosenthal 1M. Enzy-matic studies of a new variant of GMt gangliosidosis in an older child [abstract). Pediatr Res 1977;11:407. 26. Kobayashi T, Ohta M, Goto 1, Tanaka Y, Kuroiwa Y. Adult type mucolipidosis with beta-galactosidase and sialidase deficiency. JNeural 1979;221:137-49. 27. Kuriyama M, Miyatake T, Owada M, Kitagawa T. Neuraminidase activities in sialidosis and mucolipidosis. J Neural Sci 1982;54:181-7. 28. O'Brien JS. Neuraminidase deficiency in the cherry red spot-myoclonus syndrome. Biachem Biaphys Res Cammun 1977;79:1136-40. 29. O'Brien JS, Warner TG. Sialidosis: delineation of subtypes by neuraminidase assay. Clin Genet 1979;17:35. 30. Okada S, Kato TA, Miura S, et al. Hypersialyloligosacchariduria in mucolipidoses: a method for diagnosis. Clin Chim Acta 1978;86:159-67. 31. Orii T, Minami R, Sukegawa K, et al. A new type of mucolipidosis with beta-galactosidase deficiency and glycopeptiduria. Tahaku JExp Med 1972;107:303-15. 32. Quazzi GC, Ghetti B, Barberi F, Cecio A. Myoclonus-epilepsy with cherry-red spot in adult: a peculiar form of mucopolysaccharidosis. Acta Neural (Napoli) 1973;28:542-9. 33. Rapin I, Goldfisher S, Katzman R, Engel J, O'Brien JS. The cherry-red spot-myoclonus syndrome. Ann Neural 1978; 3:234-42. 34. Spranger J, Gehler J, Cantz M. Mucolipidosis I-a sialidosis. Am JMed Genet 1977;1:21-9. 35. Susuki Y, Nakamura N, Fukuoka K, Shimada Y, Uono M. Beta-galactosidase deficiency in juvenile and adult patients. Hum Genet 1977;36:219-29. 36. Swallow DM, Evans L, Stewart G, Thomas PK, Abrams JD. Sialidosis type I: cherry red spot-myoclonus syndrome with sialidase deficiency and altered electrophoretic mobility of some enzymes known to be glycoproteins. Ann Hum Genet 1979;43:27-35. 37. Symonds C. Myoclonus. Med JAust 1954;1:765-8. 38. Winter RM, Swallow DM, Baraitser M, Purkiss P. Sialidosis type 2 (acid neuraminidase deficiency): clinical and biochemical features of a further case. Clin Genet 1980;18:20310. 1, 198/~ |
