Type 2 sialidosis (ST-2) is a rare lysosomal deposit disease, and a severe form of early-onset sialidosis, characterized by a progressively severe mucopolysaccharidosis-like phenotype (rough face, multiple dysostosis, hepatosplenomegaly) and cherry red macular spots. as well as psychomotor and developmental delay. ST-2 shows a wide spectrum of clinical severity with prenatal / congenital, infantile and juvenile presentations.
Summary
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- 1 synonym
- 2 Subtypes
- 1 Congenital form
- 2 Childish form
- 3 Youth form
- 3 Epidemiology
- 4 Clinical description
- 5 Etiology
- 6 Diagnostic methods
- 1 Differential diagnosis
- 2 Prenatal diagnosis
- 7 Genetic advice
- 8 Management and treatment
- 9 Forecast
- 10 Sources
Synonymous
Dysmorphic infantile sialidosis
Subtypes
Congenital form
It manifests with generalized swelling of the fetus, neonatal ascites (accumulation of fluid in the peritoneal cavity), skeletal dysplasia (abnormal development of tissues and organs), telangiectasia (dilation of blood vessels of very small caliber), opaque cornea , hepatosplenomegaly ( liver and spleen abnormally large) and death: fetal or early infancy .
Child shape
It begins in the first year of life. They present with multiple dysostoses (deformities due to bone ossification), moderate mental retardation, seizures, splenomegaly (abnormally large vessel), corneal opacity and cherry red muscular stain, the disease being rapidly progressive. These two forms are due to an isolated neuraminidase deficiency.
Youthful form
It is due to a combined deficit of two enzymes (a protein substance capable of activating a defined chemical reaction): beta-galactosialidase and neuraminidase. The clinic is similar to the infantile form although it can appear at any time between the neonatal period and adulthood.
epidemiology
The prevalence of ST-2 is unknown. The prevalence of sialidosis (type 1 and 2 combined) has been estimated at approximately 1 / 5,000,000-1 / 1,500,000 live births.
Clinical description
ST-2 presents a wide range of clinical manifestations and is generally divided into congenital / prenatal, infantile, and juvenile forms. The congenital / prenatal form is characterized by nonimmune hydrops fetalis or ascites, presenting in utero or at birth and by the development of a mucopolysaccharidosis-like phenotype that includes rough face features, multiple dysostosis, hepatosplenomegaly , and umbilical and inguinal hernias. Children who survive and those affected by the infantile onset form (before 12 months of age) are characterized by a mucopolysaccharidosis-like phenotype that includes rough face, multiple dysostosis, kyphosis., short stature (with slow growth by 18 months of age), hepatosplenomegaly, hearing impairment, cherry red spots on the retina (a constant feature after 3 years of age), corneal opacity (rare), and delayed speech and development, followed by psychomotor regression and myoclonus and ataxia in some cases. Kidney disease (nephrosialidosis) has been described in some affected patients. The juvenile form usually presents after two years of age with a rough face with less pronounced features, angiokeratoma , myoclonic seizures, cherry red macular spots, and psychomotor regression.
Etiology
ST-2 is due to a mutation in the N-acetyl-alpha-neuraminidase-1 (NEU1) gene (6p21) that codes for the lysosomal enzyme neuraminidase, which initiates the degradation of sialoglycoconjugates in lysosomes . Mutations lead to a deficiency of enzyme activity and, as a consequence, an accumulation of siallyl oligosaccharides in tissues. In general, increased residual neuramine activity is associated with milder symptoms and longer life expectancy.
Diagnostic methods
An ophthalmological examination (fundoscopy) may reveal cherry red bilateral macular spots. Neuroimaging techniques show varying degrees of cerebral and cerebellar atrophy. The diagnosis is suspected by detecting the excretion of sialyl oligosaccharides in urine and should be confirmed by demonstration of the deficiency of the enzyme neuraminidase (in the presence of normal beta-galactosidase activity) in leukocytes or preferably in fibroblast cultures. Molecular genetic tests showing causal mutation (s) can also confirm the diagnosis. The presence of ultrasound signs (such as dropsy , edema , ascites) can contribute to the diagnosis of prenatal forms during pregnancy .
Differential diagnosis
The main differential diagnosis includes galactosialidosis (characterized by deficiencies of both beta galactosidase and neuraminidase) and mucopolysaccharidosis type 1, 2, or 6. Many individuals in the juvenile subgroup, in particular, may appear to have a form of galactosialidosis.
Prenatal diagnosis
Prenatal diagnosis can be performed by measuring enzyme activity or by molecular genetic testing if the underlying molecular defect in the family is well characterized.
Genetic advice
ST-2 follows an autosomal recessive form of inheritance. Genetic counseling is possible.
Management and treatment
There is no cure for ST-2 and management is multidisciplinary, mainly involving palliative care. Anticonvulsants can be used to treat myoclonic seizures, but they are rarely effective. Hemapotoytic stem cell transplantation has failed to successfully prevent psychomotor regression, bone changes, or nephrosialidosis.
Forecast
The prognosis depends on the type of ST-2. The congenital form produces stillbirth or death in the first two years of life. For the other forms, life expectancy generally does not exceed two decades.
