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Sialidosis type 1
Sialidosis type 1 (ST-1) is a very rare lysosomal storage disease, and is the normosomatic form of sialidosis (see this term), characterized by gait abnormalities, progressive visual loss, bilateral macular cherry red spots and myoclonic epilepsy and ataxia, that usually presents in the second to third decade of life.
ORPHA:812Classification level: Disorder
The prevalence of ST-1 is unknown but it is less frequent than sialidosis type 2 (ST-2, see this term). The prevalence of sialidosis (types 1 and 2 combined) has been estimated at approximately 1/5,000,000-1/1,500,000 live births.
The disease usually presents in adolescence (onset usually between 12 and 25 years) with gait disturbance, walking difficulties and/or a loss of visual acuity. Almost all patients display a cherry-red spot on the retina. They may also have generalized myoclonus, in some cases associated with seizures and ataxia. Color vision progressively diminishes while night blindness appears and, in some cases, corneal opacities and nystagmus are present. Intellectual capacity is normal. In contrast to ST-2, patients do not show facial dysmorphism, bone dysplasia or psychomotor retardation.
ST-1 is due to a mutation of the N-acetyl-alpha-neuraminidase-1 (NEU1) gene (6p21) encoding the lysosomal enzyme neuraminidase, that initiates the degradation of sialoglycoconjugates in lysosomes. Mutations lead to a decrease in enzyme activity and consequently to an accumulation of sialyloligosaccharides in tissues. Disease severity is linked to level of residual neuraminidase activity in vivo and varies between patients.
An ophthalmological examination (fundoscopy) can visualize bilateral cherry-red spots. Magnetic resonance imaging of the brain can reveal diffuse brain atrophy in advanced cases, but is usually normal on first examination. Detection of urinary sialyloligosaccharides can be suggestive of a diagnosis, but excretion levels may be quite low. The diagnosis must be confirmed by the demonstration of deficient neuraminidase activity (in the presence of normal beta-galactosidase activity) in leukocytes or, preferably, in cultured fibroblasts. Diagnosis can be confirmed by molecular genetic testing revealing mutations in the NEU1 gene.
The main differential diagnosis is galactosialidosis (see this term), which is characterized by deficiencies in both neuraminidase and beta-galactosidase.
Prenatal diagnosis can be performed by enzyme activity measurement or by molecular genetic analysis if the underlying molecular defect in the family is well established.
ST-1 is inherited in an autosomal recessive manner. Genetic counseling is possible.
Management and treatment
There is no cure for ST-1 and management should be multidisciplinary to allow for adapted symptomatic treatment, which is essential for improving the quality of life of affected patients. In severe cases, patients may require the use of a wheelchair.
There appears to be no major effect on life expectancy but quality of life can be affected due to myoclonus and resulting mobility issues.