Diagnosis and Management of Type 1 Sialidosis: Clinical Insights from Long-Term Care of Four Unrelated Patients

Abstract

Background: Sialidosis is a rare autosomal recessive disease caused by NEU1 mutations, leading to neuraminidase deficiency and accumulation of sialic acid-containing oligosaccharides and glycopeptides into the tissues. Sialidosis is divided into two clinical entities, depending on residual enzyme activity, and can be distinguished according to age of onset, clinical features, and progression. Type 1 sialidosis is the milder, late-onset form, also known as non-dysmorphic sialidosis. It is commonly characterized by progressive myoclonus, ataxia, and a macular cherry-red spot. As a rare condition, the diagnosis is often only made after few years from onset, and the clinical management might prove difficult. Furthermore, the information in the literature on the long-term course is scarce. Case presentations: We describe a comprehensive clinical, neuroradiological, ophthalmological, and electrophysiological history of four unrelated patients affected by type 1 sialidosis. The long-term care and novel clinical and neuroradiological insights are discussed. Discussion and conclusions: We report the longest follow-up (up to 30 years) ever described in patients with type 1 sialidosis. During the course, we observed a high degree of motor and speech disability with preserved cognitive functions. Among the newest antiseizure medication, perampanel (PER) was proven to be effective in controlling myoclonus and tonic–clonic seizures, confirming it is a valid therapeutic option for these patients. Brain magnetic resonance imaging (MRI) disclosed new findings, including bilateral gliosis of cerebellar folia and of the occipital white matter. In addition, a newly reported variant (c.914G > A) is described.

Fluorescent In Situ Staining and Flow Cytometric Procedures as New Pre-Diagnostic Tests for Sialidosis, GM1 Gangliosidosis and Niemann–Pick Type C

“…These three neurodegenerative conditions are very rare, with an approximate prevalence of 1/5,000,000-1/1,500,000 live births for Sialidosis (OMIM #256550)[ 4 ], 1:100,000–1:200,000 live births for GM1 gangliosidosis (OMIM #230500) [ 5 , 6 ], and from 0.35 to 2.2 per 100,000 births, depending on the geographic area, for NPC (OMIM #257220) [ 7 ]. The mild form of sialidosis Type I, whose clinical presentation is mostly confined to ophthalmologic problems and myoclonus, and the juvenile/adult forms of GM1 gangliosidosis are probably underestimated and likely to be more common than reported [ 8 , 9 ].…”

Sialidosis type 1 without cherry-red spots: a case report and literature review

“…However, Bou Ghannam AS et al reported a case where no cherry-red spots were observed in the fundus 10. Likewise, Coppola et al observed patients for as long as 30 years and found no cherry-red spots in the fundus 11. Therefore, while cherry-red spots may appear in type I sialidosis, using it to name the disease is imprecise and may mislead clinicians in making early diagnoses.…”

NEU1—A Unique Therapeutic Target for Alzheimer’s Disease

“…Additionally, decreased connectivity from the temporal and occipital lobes to the hippocampus and para-hippocampus has also been noted. Moreover, a compromised posterior visual pathway, with extensive involvement of the brain’s posterior part, has been related to cortical blindness in sialidosis I patients ( Lai et al, 2009 ; Sobral et al, 2014 ; Lu et al, 2017 ; Gultekin et al, 2018 ; Hu et al, 2018 ; Coppola et al, 2020 ).…”

“…Type I sialidosis is the less severe form, with a late onset of symptoms ( d’Azzo et al, 2015 ). Typical symptoms of type I sialidosis, also known as cherry-red spot myoclonus syndrome, include progressive visual loss, bilateral cherry-red spots, and myoclonus, and are generally manifested during adolescence ( Coppola et al, 2020 ). Type II sialidosis, in contrast, takes a more severe course and is further subdivided into three subtypes.…”