Sialidosis is an autosomal recessive disease that belongs to a family of disorders identified as lysosomal storage diseases. This disorder is characterized by the lysosomal accumulation of sialyloligosaccharides derived from glycoproteins and glycolipids as a consequence of defects in the lysosomal hydrolase, neuraminidase (also referred to as sialidase). Deficiency in neuramindase is also associated with galactosialidosis (also referred to as Goldberg syndrome).
The neuraminidase gene (NEU1) is a small gene located on chromosome 6p21.3 spanning only 3.5 kb comprising 6 exons encoding a 415 amino acid glycoprotein. Neuramindase has a dual function, it is involved in lysosomal degradation of sialylated glycoconjugates as well as in cellular immune responses. Functional neuramindase is found in a multisubunit complex with β-galactosidase (GLB1) and protective protein/cathepsin A (PPCA). Deficiency in β-galactosidase results in GM1 gangliosidosis. Neuraminidase functions in the regulation of immune responses primarily through it's action on specialized antigen-presenting cells called dendritic cells (DCs). The action of neuramindase on DCs leads to their activation and maturation, thus enhancing immune responses to foreign antigen.
Clinically, sialidosis patients can be divided into two types. Type I sialidosis is the more mild form of the disease. Type II sialidosis is further divided into congenital, infantile and juvenile forms.
Patients with type I sialidosis appear normal for the first 20 to 30 years of life. Symptoms that bring attention to the this form of the disease is the development of walking difficulties and/or the loss of visual acuity. As a consequence of ophthalmic examination to address the vision problems, the presence of ocular cherry-red spots (as described for Tay-Sachs disease) becomes apparent. In fact, so common is this clinical finding in type I sialidosis that the disease is often referred to as the cherry-red spot-myoclonus syndrome.
Type II sialidosis symptoms are more severe and present much earlier than in type I disease. All three forms of type II sialidosis are associated with coarse facial features and mental retardation. The congenital form is evident in utero, the infantile form manifests between birth and 12 months of age and the juvenile form manifests after 2 years of age. Because deficiencies in neuramindase are associated with sialidosis and galactosialidosis it may be that those patients defined as type II juvenile may in fact be afflicted with galactosialidosis. The congenital form of the disorder is associated with hydrops fetalis and afflicted fetuses are stillborn. All patients with type II sialidosis will develop a progressive severe phenotype including mental retardation and dystosis multiplex. Dystosis multiplex represents a constellation of skeletal abnormalities characterized by an enlarged skull, thickened calvarium, premature closure of lamboid and sagittal sutures, shallow orbits, enlarged J-shaped sella turcica (a saddle-shaped skull structure into which sits the bottom of the pituitary gland), and abnormal spacing of the teeth with dentigerous cysts. There is anterior hypoplasia of the lumbar vertebrae, the long bone diaphyses are enlarged and an irregular appearance of the metaphyses. The epiphyseal centers not well developed, the pelvis is poorly formed with small femoral heads and coxa valga. The clavicles are short, thick and irregular and the ribs are oar shaped. Phalanges are shortened and trapezoidal in shape.