Sialidosis (Mucolipidosis I) Clinical Presentation
- Author: Karl S Roth, MD; Chief Editor: Luis O Rohena, MD more...
In general, sialidosis is a heterogenous disorder with a wide spectrum of variability in disease manifestation.
Patients with the type II infantile form may be normal or almost normal in appearance at birth. Coarse facial features, developmental delay, and hepatosplenomegaly may develop within the first year of life.
Although not as severe as the Hurler phenotype, similar-appearing coarse features, hepatosplenomegaly, and skeletal abnormalities (dysostosis multiplex) become more pronounced with time. Short stature may also progressively develop.
The extent of neurologic progression varies, but macrocephaly, hypotonia, nystagmus, visual impairment, and myoclonic seizures are known to develop. Cherry-red spots appear with age in most patients. As the neurologic picture progresses, these patients become nonambulatory and are unable to care for themselves.
In the congenital form, hepatosplenomegaly, ascites, and hydrops fetalis are noted at birth, and the infant may be stillborn. In those who survive postnatally, the course is rapidly progressive.
Nephrosis has been reported in some patients; these patients may comprise a subgroup of the infantile form.
Patients with the adult form of the disease first report visual impairment due to color blindness or night blindness. Cherry-red spots are present in virtually all such patients. Myoclonus, which can be disabling, and ataxia develop later.
Neurologic findings include the following:
Developmental delay or mental retardation
Visual impairment or loss of visual acuity
Nystagmus, ataxia, and seizures (have been reported)
Coarse facial features include the following:
High forehead, puffy eyelids, epicanthal folds
Flat nasal bridge, anteverted nares, long philtrum
Gingival hypertrophy, macroglossia
Skeletal abnormalities include the following:
Lumbar gibbus deformity and kyphoscoliosis
Joint stiffness and contractures (may develop)
Ophthalmologic findings include cherry-red macula, corneal opacities, lens opacities, and lamellar cataracts. Abdominal findings include hepatosplenomegaly in patients with the type II form as a result of visceral storage. Findings in the congenital form include hydrops fetalis, neonatal ascites, hepatosplenomegaly, and inguinal hernia.
Sialidosis is an autosomal recessive disorder caused by an isolated deficiency of the enzyme, alpha-N -acetyl neuraminidase (also called sialidase). Three distinct human neuraminidases are known and are specifically localized to the cytosol, plasma membrane, and lysosome. The lysosomal enzyme is selectively deficient in human sialidosis. The lysosomal neuraminidase gene maps to chromosome 6p21 and has been cloned. Various enzyme-inactivating mutations have been identified in patients with sialidosis.
The variability of disease manifestation due to this enzyme deficiency, as evidenced by the 3 disease subtypes, has indicated a potential genotype-phenotype correlation. Research has shown that the type of gene mutation affects not only enzyme activity but also whether the enzyme localizes to the lysosome. Preliminary studies indicate that both of these properties have positively correlated with the clinical subtype of sialidosis. However, the wide variability of clinical presentation in these patients cannot be fully explained by alpha-N -acetyl neuraminidase mutations. Therefore, other environmental or genetic factors probably account for the varying degrees of disease severity.
More than 40 mutations in the NEU1 gene have been described. Most are missense mutations, but deletions and insertions have also been described. In multiple small studies, sequencing identified all mutations in the NEU1 gene.[4, 5, 6]
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