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  • Updated 06.21.2022
  • Released 02.03.1994
  • Expires For CME 06.21.2025

Sialidosis

Introduction

Overview

Sialidosis is an autosomal recessive lysosomal storage disorder caused by deficiency of neuraminidase 1 due to NEU1 mutations. Sialidosis type I is characterized by the development of ocular cherry-red spots and generalized myoclonus in the second or third decade of life. Seizures, hyperreflexia, ataxia, and progressive atrophy on brain MRI may also occur. Sialidosis type II is more severe than type I and is distinguished by the early onset of a progressive, mucopolysaccharidosis-like phenotype with visceromegaly, dysostosis multiplex, and intellectual disability. In severe cases, hydrops fetalis may occur.

Key points

• Sialidosis is a disorder of sialic acid metabolism.

• It is often associated with myoclonic epilepsy in juveniles or young adults, sometimes without visual impairment.

• Eye and skeletal abnormalities may be helpful for the diagnosis.

• Macular cherry-red spots may occur in otherwise asymptomatic patients or be absent in symptomatic patients.

Historical note and terminology

Sialidosis is a disorder resulting from an inherited, isolated deficiency of neuraminidase 1 (sialidase) (35; 51; 05; 15). Because the first patients shown to suffer from this enzyme abnormality had originally been included in a group of patients given the designation "mucolipidosis" (69), this disorder is also sometimes referred to as mucolipidosis I (68). The enzyme defect was first demonstrated in this group of patients in 1977 (13; 68). Within a year, several investigators independently described an adult group of patients with deficiencies of neuraminidase 1 activity (18; 50; 58; 73). The late-onset form of the disorder, originally labeled the cherry-red spot-myoclonus syndrome, is now referred to as sialidosis type I.

Sialidosis (mucolipidosis I) is not to be confused with mucolipidosis II (I-cell disease) or mucolipidosis III (pseudo-Hurler polydystrophy). Although patients with these latter disorders are also characterized by neuraminidase deficiencies, the defect is neither a primary nor an isolated abnormality. Rather, the neuraminidase deficiencies in mucolipidosis II and III are the secondary result of defective post-translational modification involving many lysosomal enzymes (49). Mucolipidosis IV, although sharing the same name, is also a distinct and genetically unrelated disorder. It is caused by mutations in MCOLN1 that codes for a protein called mucolipin 1, thought to be a cationic ion channel (61).

The classification of sialidosis is also complicated by the existence of a combined neuraminidase and beta-galactosidase deficiency, generally referred to as galactosialidosis (52). Various studies, such as somatic cell hybridization and biochemical and genetic mapping, have demonstrated that sialidosis and galactosialidosis result from mutations of different genes and are, thus, two distinct disorders.

Sialidosis must be distinguished from sialuria, the term given to patients who excrete excessive amounts of free sialic acid due to the defective feedback control of UDP-GlcNAc 2-epimerase, leading to hypersialylated O-glycans (34; 85). Finally, sialidosis patients should not be confused with those patients suffering from free sialic storage disease or Salla disease, both of which are the result of the defective transport of sialic acid across lysosomal membranes (04).

In an early review, Lowden and O'Brien proposed that patients with a primary neuraminidase 1 deficiency could be divided into two groups (35). They classified the more mildly affected patients, those who lacked physical changes (normosomatic), as sialidosis type I. The more severely affected patients, having obvious physical changes (dysmorphic), were designated as sialidosis type II. These broad categories have been further subdivided (51).

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