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

Antonietta Coppola,Francesca Simonelli,Marta Bellofatto,Pasquale Striano,Settimio Rossi,Betul Baykan,Barbara Castellotti,Lorenzo Ugga,Salvatore Striano,Ebru N Vanli-Yavuz,Marta Ianniciello,Alessandra D’Amico,Serena Troisi,Marcello Esposito,Leonilda Bilo,Stefano Tozza

doi:10.3390/brainsci10080506

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.

Highlights

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
We have reported the clinical, neuroradiological, ophthalmological, and electrophysiological course of four unrelated patients affected by type 1 sialidosis, bearing compound heterozygosity of
We reported the long-term follow-up and detailed clinical history of four patients affected by type 1 sialidosis, supporting it with neurophysiological data, as well as brain and ophthalmological images

Summary

Introduction

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. Type 1 sialidosis is the milder, late-onset form, known as non-dysmorphic sialidosis It is commonly characterized by progressive myoclonus, ataxia, and a macular cherry-red spot. As myoclonus is the key symptom being present in 100% of the patients, type 1 sialidosis is considered among the progressive myoclonus epilepsies (PMEs) This group of conditions are neurophysiologically characterized by cortical hyperexcitability demonstrated by the evidence of a giant somatosensory evoked potential (SEP); the presence of the long loop reflex (LLR), known as C-reflex at rest; and a time-locked cortical potential preceding electromyography (EMG) bursts evidenced by the jerk-locked back averaging analysis (JL-Back AVG) [4,5]

Results

Discussion

Conclusion