Neuraminidase Deficiency
Patient Information
Characteristics
Background and History
Neuraminidase deficiency, sometimes labeled sialidosis, or mucolipidosis, is one of numerous hereditary lysosomal storage disorders. Lysosomes are small organelles within cells in which important metabolic reactions take place. These reactions are usually dependent on enzymes that break down molecules and when these malfunction as the result of gene mutations, certain products accumulate with deleterious effects on the cells.
Clinical Correlations
The defect in this disorder is in an enzyme known as neuraminidase, resulting in an accumulation of glycoproteins which are complex molecules of sugar and protein. Several types of this disorder have been described including congenital, infantile, juvenile and adult forms with classification based mainly on the age of onset. An early onset such as during the first year of life carries a poor prognosis with an early death and is often designated type II. Type I has a later onset with milder disease and usually causes less intellectual damage. Life expectancy may be near normal in older individuals with mild disease.
The characteristic features are relatively coarse facial features, an enlarged tongue, spinal deformities, and an enlarged liver and spleen. Muscle tone may be poor but reflexes are brisk. Muscle weakness is common and often progressive leading to difficulties in walking. The majority of patients have cognitive deficits especially those with an early onset of disease. Some patients have a hearing defect and most have vision loss and some colorblindness due to damage to cells in the retina. Clouding of the cornea and lens opacities (cataracts) are often seen. The disorder is a progressive one and mental and physical functions worsen with age.
Genetics
Inheritance
All types of neuraminidase deficiency are inherited in autosomal recessive patterns because they require the presence to two mutations in the gene. Parents, who carry only one copy, are usually normal but each of their children have a 25% risk of inherited both copies and therefore the disease.
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
Diagnosis and Prognosis
The diagnosis is usually made by a pediatrician in consultation with a neurologist and a medical geneticist. An ophthalmologist can help confirm the diagnosis by examination of the eyes. Treatment is focused on symptoms such as physical therapy and special education. Low vision aids can be helpful for older individuals with mild vision loss.
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