# Sphingolipidoses and Retinal Involvement: A Comprehensive Review
## 4 Subtypes of Sphingolipidoses
### 4.9.3.1 Disease Pathogenesis and Systemic Symptoms
#### 4.9.2 Retinal Manifestations  
Sialidosis types 1 and 2 can present with ocular involvement, characterized by manifestations such as nystagmus, corneal clouding resulting from the accumulation of metabolic byproducts, cataracts and optic nerve atrophy [32; 33; 36; 159]. In the congenital form of type 2 sialidosis, bilateral congenital cataracts are frequently observed, along with foveal hypoplasia [152]. From a retinal perspective, the most distinctive finding in both type 1 and type 2 sialidosis is the presence of bilateral macular cherry-red spots, attributed to the pathological accumulation of lipidic material within the retinal ganglion cells. This feature is considered a key hallmark of the disease [33]. SD-OCT imaging corroborates these findings, revealing thickening of GCL with areas of increased reflectivity [158]. Over time, a paradoxical reduction in this ophthalmoscopic sign may occur, likely due to progressive ganglion cell degeneration [151]. The accumulation of sialyloligosaccharides has been identified in type 1 sialidosis, within the peripapillary RNFL, where an increase in thickness may be observed [33]. Some authors suggested that, in mild forms of type 1 sialidosis, the cherry-red macula represents the earliest clinical manifestation, highlighting its significance as a key diagnostic marker for early detection [163]. However, this claim is contradicted by other studies indicating that this finding appears only after several years of symptomatic disease progression [164]. \begin{table}
\begin{tabular}{p{56.9 pt} p{56.9 pt} p{56.9 pt} p{56.9 pt} p{56.9 pt}} \hline
**Disease** & **Defective Enzyme (Mutated Gene)** & **Primary Storage Compound** & **Systemic Symptoms and Manifestations** & **Ocular Manifestations (Non-Retinal and Retinal Manifestations)** \\ \hline
**Sialidosis type 1** (1:5,000,000-1:5,000,00) [157] & N-acetyl-alpha-neuralinidase-1 (NEU1 gene) [156] & Sialoglyoconjugates [156] & **Mild form (onset during adolescence)**: absence of facial dysmorphisms, normal intellectual ability, myoclous, intentional tremors, cerebellar ataxia, gait abnormalities, oligosaccharidescharduria [36; 157] & **Non retinal manifestations**: bilateral macular cherry-red spots [32; 156], Bergmeister’s papilla [158], optic nerve atrophy [159] \\ \hline
**Sialidosis type 2** (1:1,500,000-1:5,000,000) [157] & N-acetyl-alpha-neuralinidase-1 (NEU1 gene) [156] & Sileoglyoconjugates [156] & **Severe form** & **Severe form** \\  & & & & **congenital or hydropo: facial dysmorphisms, oocytes and edema, inguinal hernias, hepatosplemomegaly, hydrophcephalus telingacetylas, petechiae & **Non retinal manifestations**: foveal hypoplasia [152] bilateral macular cherry-red spots [162] \\
**Sialidosis type 2** (1:1,500,000-1:5,000) [157] & N-acetyl-alpha-neuralinidase-1 (NEU1 gene) [156] & Sialoglyoconjugates [156] & **Minfantile/juvenile**: coarse facial dysmorphisms, severe mental retardation, hepatosplemomegaly, dysmosis, hairling loss, ap  
SD-OCT based assessment of accumulated pathological material may serve as a valuable tool for monitoring disease progression [163]. A single case of Bergmeister's papilla was reported in type 1 sialidosis, characterized by an epippillary glial membrane that appeared as a whitish area of vitreous thickening on fundoscopic examination. Although typically asymptomatic, its presence required clinical monitoring, as contraction of the membrane may, in rare cases, lead to tractional retinal detachment [158]. A potential association between type 1 sialidosis and choroidal hyperpermeability has been proposed. In a patient presenting with bilateral cherry-red macula and retinal pigment epithelial detachment (PED) with subretinal fluid detected via SD-OCT, indocyanine green angiography revealed a hypocyanescent parafovea, potentially linked to inner retinal layer hyperreflectivity, along with a hypercyanescent fovea, possibly associated with choroidal hyperpermeability.