Title | Sialidosis Type 1 Without Cherry-Red Spot |
Creator | Alaa S. Bou Ghannam; Lauren C. Mehner; Victoria S. Pelak |
Affiliation | Departments of Ophthalmology (ASBG, LCM, VSP); and Neurology (ABG, VSP), University of Colorado School of Medicine, Aurora, Colorado |
Abstract | Sialidosis is an autosomal recessive lysosomal storage disease caused by mutations in the neuraminidase 1 (NEU1) gene located on 6p21.33 chromosome leading to low levels of alpha-N-acetylneuraminidase (sialidase) and accumulation of sialyloligosaccharides. |
Subject | Adult; Diagnostic Techniques, Ophthalmological; Eye Movement Measurements; Humans; Male; Mucolipidoses / diagnosis; Mucolipidoses / physiopathology; Tomography, Optical Coherence |
OCR Text | Show Clinical Correspondence Sialidosis Type 1 Without Cherry-Red Spot Alaa S. Bou Ghannam, MD, Lauren C. Mehner, MD, Victoria S. Pelak, MD S ialidosis is an autosomal recessive lysosomal storage disease caused by mutations in the neuraminidase 1 (NEU1) gene located on 6p21.33 chromosome leading to low levels of alpha-N-acetylneuraminidase (sialidase) and accumulation of sialyloligosaccharides (1). Of the 2 types of sialidosis, Type 2 is similar to mucolipidosis-I with Hurler-like symptoms including mental retardation, cloudy cornea, and dysmorphic features (1). Type 1 sialidosis (known as cherry-red spot-myoclonus syndrome) presents in the second decade of life with less severe vision loss and myoclonus (1). A macular cherry-red spot has been suggested to be a crucial manifestation-hence the name (2). Here, we describe a patient with sialidosis Type 1 presenting with punctate cataracts, periodic alternating nystagmus (PAN), skew deviation, optic nerve cupping, and absence of a macular cherry-red spot. CASE PRESENTATION A 25-year-old man of Hispanic origin developed physical and cognitive decline around age 9 years. By age 12 years, he was increasingly ataxic with frequent falls. He developed lower extremity "tremors" by age 15 and vision difficulties at age 17 when he presented to the emergency department after syncope. His examination revealed marked hyperreflexia, ataxia, and tremor. There was hyperbilirubinemia noted on laboratory testing. The patient underwent liver biopsy with initial concern for possible mitochondrial disease. Increased sialic acid levels were identified in his white blood cells. Low sialidase levels (0.7445 nmol/mg protein; normal 4.5-83.3) and skin fibroblast pathology were consistent with the diagnosis of sialidosis Type 1. Initial ophthalmic examination at age 17 years showed visual acuities of 20/70 in the right eye and 20/50 in the left eye, no stereopsis, decreased color vision, and no afferent pupillary defect. There were normal anterior segment and fundus examinations with cup-to-disc ratios of 0.2. The examiners reported nystagmus without a more detailed description. The patient had an ectropion of the left lower Departments of Ophthalmology (ASBG, LCM, VSP); and Neurology (ABG, VSP), University of Colorado School of Medicine, Aurora, Colorado. The authors report no conflicts of interest. Address correspondence to Alaa S. Bou Ghannam, MD, Department of Neurology, University of Colorado School of Medicine, 12631 East 17th Avenue, Aurora, CO 80045; E-mail: alaa.bghannam@gmail.com 388 eyelid that was presumed to be due to excision of an unknown eyelid mass while living in Mexico. At age 21 years, genetic testing revealed a c.C880T, p.R294C missense mutation in the NEU1 gene on chromosome 6p21.33; this confirmed the diagnosis of sialidosis Type 1. He presented to our neuro-ophthalmology service at age 25 years for progressive decline in vision, nyctalopia, oscillopsia, and intermittent, bilateral, monocular double vision. The patient was on no medications. Examination showed best-corrected visual acuities of 20/200 in the right eye and 20/150 in the left eye. He had no stereopsis by the fly test and was unable to perceive any of the Hardy-RandRittler color plates. Ocular motility examination revealed an esophoria (4 prism diopters) at distance, an exophoria at near (3 prism diopters), and an alternating skew deviation (2 prism diopter right hypertropia in right gaze and 1 prism diopter left hypertropia in left gaze). He had PAN with direction change every 90 seconds and a 10-second pause; there were a few downbeat fast phases before the shift in direction and null point. External examination showed down slanting of eyelid fissures, mild laxity of both eyelids, mild ptosis, and absence of lid creases. The patient had ectropion of the left lower eyelid. The anterior segment was normal except for bilateral punctate lenticular lesions. The fundus examination showed normal macula with absence of a cherry-red spot. The optic discs were cupped with a 0.7 cup-to-disc ratio; there was no pallor or swelling (Fig. 1). Optical coherence tomography (OCT) showed mild thickening of the perifoveal macular areas bilaterally (Fig. 2). Fundus autofluorescence showed perifoveal hyperautofluourescence (Fig. 1). MRI of the brain demonstrated moderate cerebellar atrophy. DISCUSSION Our patient satisfied the genetic and tissue criteria for the diagnosis of sialidosis Type I, but his presentation was atypical given the lack of a macular cherry-red spot and the presence of PAN as well as abnormal liver function. Macular cherry-red spot is present in several lysosomal storage diseases caused by deposition of material in the ganglion cells at the macula. The absence of ganglion cells in the fovea makes this region relatively transparent and contrasting with the surrounding opaque retina. Thus, a better name might be "perifoveal white patch" (1). Such Bou Ghannam et al: J Neuro-Ophthalmol 2019; 39: 388-390 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 1. Fundus photographs of both eyes showing absence of a cherry-red spot and cupping of the optic nerves (A) and fundus autofluorescence showing perifoveal hyperfluorescence and punctate shadows from the cataract (B). macular thickening with sparing of the fovea is further demonstrated with OCT imaging (3). Some reports have stated that a macular cherry-red spot is present in all cases of sialidosis Type 1 (1,2). Other reports, however, suggest that it can be absent early in the course of disease, similar to what is seen in Tay-Sachs disease (3,4). Canafoglia et al reported 6 patients from 2 families who were diagnosed with sialidosis based on genetic testing; none of these individuals had macular cherry-red spots (5). Lai et al reported that macular cherry-red spots were present in 3 of 17 Taiwanese patients with sialidosis Type 1 with the Ser182Gly mutation (6). We suggest 3 possibilities that could explain the absence of a cherry-red spot in our patient. First, given the Hispanic heritage, the macular cherry-red spot might be subtle because his fovea is less transparent than in previously described patients. This may explain the patient's low vision that is comparable with that of patients with macular cherry-red spot. Alternatively, or in combination, the ganglion cell loss may have been severe enough to result in loss of distinction between the fovea and surrounding region; this is possible because the patient had progressive cupping of the optic disc over time (from 0.2 to 0.7) without evidence of glaucoma. However, this change in the cup-to-disc ratio happened later in the disease course. Ophthalmic examination from 8 years prior did not show any evidence of a macular cherry-red spot. Furthermore, the macular thickness was actually mildly increased. Finally, the patient's specific mutation may be less likely to be associated with Bou Ghannam et al: J Neuro-Ophthalmol 2019; 39: 388-390 a macular cherry-red spot. Our patient's mutation has been reported only once previously in a report of a patient from India; however, that patient did have a cherry-red spot (7). Nystagmus has been reported with sialidosis Type I, although there is no specific report of PAN (1,2). This type of nystagmus is not a surprising finding given the documented cerebellar atrophy. Regarding our patient's cataracts, a variety of different types of lenticular opacifications have been described, including punctate cataracts (1). Optic atrophy and increased cup-to-disc ratio have been suggested, although no clear reports are present in the literature (2). Another peculiar and nonophthalmological finding in our patient was the elevated bilirubin level. No other reported cases of sialidosis have had liver involvement. At this point, it would be difficult to know whether this feature is related to the sialidosis disease or to a separate entity. In conclusion, we suggest that "cherry-red spotmyoclonus syndrome" may not be most inclusive term to describe sialidosis Type 1. Although a macular cherry-red spot is present in previously reported cases, our report confirms that it is possible for this finding to be absent. Symptoms of sialidosis can vary from infantile death (Type 2) to myoclonus and normal life span (Type 1). Similarly, ocular manifestations can vary along a spectrum and typically involve cherry-red spot in most, but not all cases. Cataracts, nystagmus, ocular misalignment, corneal opacities, increased cup-to-disc ratio, optic atrophy, and external eye anomalies may also be present. 389 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 2. Optical coherence tomography scans of the macula showing perifoveal thickening. ETDRS, Early Treatment Diabetic Retinopathy Study. STATEMENT OF AUTHORSHIP Category 1: a. conception and design: Alaa S. Bou Ghannam, Victoria Pelak, and Lauren C. Mehner; b. acquisition of data: Alaa S. Bou Ghannam, Victoria Pelak, and Lauren C. Mehner; c. analysis and interpretation of data: Alaa S. Bou Ghannam, Victoria Pelak, and Lauren C. Mehner. Category 2: a. drafting the manuscript: Alaa S. Bou Ghannam, Victoria Pelak, and Lauren C. Mehner; b. revising it for intellectual content: Alaa S. Bou Ghannam, Victoria Pelak, and Lauren C. Mehner. Category 3: a. final approval of the completed manuscript: Alaa S. Bou Ghannam, Victoria Pelak, and Lauren C. Mehner. REFERENCES 1. Sobral I, Cachulo Mda L, Figueira J, Silva R. Sialidosis type I: ophthalmological findings. BMJ Case Rep. 2014;2014:2014. 390 2. Till JS, Roach ES, Burton BK. Sialidosis (neuraminidase deficiency) types I and II: neuro-ophthalmic manifestations. J Clin Neuroophthalmol. 1987;7:40-44. 3. Kersten HM, Roxburgh RH, Danesh-Meyer HV, Hutchinson DO. Optical coherence tomography findings in a patient with type 1 sialidosis. J Clin Neurosci. 2016;31:199-201. 4. Kivlin JD, Sanborn GE, Myers GG. The cherry-red spot in Tay-Sachs and other storage diseases. Ann Neurol. 1985;17:356-360. 5. Canafoglia L, Robbiano A, Pareyson D, Panzica F, Nanetti L, Giovagnoli AR, Venerando A, Gellera C, Franceschetti S, Zara F. Expanding sialidosis spectrum by genome-wide screening: NEU1 mutations in adult-onset myoclonus. Neurology. 2014;82:2003-2006. 6. Lai SC, Chen RS, Wu Chou YH, Chang HC, Kao LY, Huang YZ, Weng YH, Chen JK, Hwu WL, Lu CS. A longitudinal study of Taiwanese sialidosis type 1: an insight into the concept of cherryred spot myoclonus syndrome. Eur J Neurol. 2009;16:912-919. 7. Ranganath P, Sharma V, Danda S, Nandineni MR, Dalal AB. Novel mutations in the neuraminidase-1 (NEU1) gene in two patients of sialidosis in India. Indian J Med Res. 2012;136:1048-1050. Bou Ghannam et al: J Neuro-Ophthalmol 2019; 39: 388-390 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. |
Date | 2019-09 |
Language | eng |
Format | application/pdf |
Type | Text |
Publication Type | Journal Article |
Source | Journal of Neuro-Ophthalmology, September 2019, Volume 39, Issue 3 |
Collection | Neuro-Ophthalmology Virtual Education Library - Journal of Neuro-Ophthalmology Archives: https://novel.utah.edu/jno/ |
Publisher | Lippincott, Williams & Wilkins |
Holding Institution | Spencer S. Eccles Health Sciences Library, University of Utah, 10 N 1900 E SLC, UT 84112-5890 |
Rights Management | © North American Neuro-Ophthalmology Society |
ARK | ark:/87278/s60635d5 |
Setname | ehsl_novel_jno |
ID | 1595897 |
Reference URL | https://collections.lib.utah.edu/ark:/87278/s60635d5 |