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A cherry red spot is may be seen in late childhood or early adolescence. It occurs in nearly 100% of patients with type I while only 75% of type II patients have this feature possibly because their early death from the more severe systemic disease prevents full ascertainment. Visual acuity is reduced, sometimes severely. Some but not all individuals have corneal and lens opacities. A subtle corneal haze has also been seen. Nystagmus has been reported.
This is a neurodegenerative disorder with progressive deterioration of muscle and central nervous system functions. Myoclonus, mental deterioration, hepatosplenomegaly, muscle weakness and atrophy are common. The defect in neuraminidase activity leads to abnormal amounts of sialyl-oligosaccharides in the urine. Spinal deformities such as kyphosis are common. Deep tendon reflexes are exaggerated. Ataxia and hearing loss may be present. Coarse facies, a barrel chest, and short stature are characteristic. Hepatic cells contain numerous vacuoles and numerous inclusions.
Sialidosis types I and II are both caused by mutations in the neuroaminidase gene. Type I is associated with milder disease than type II which has an earlier age of onset and may present in infancy or even begin in utero. Early death within two years of age is common in the congenital or infantile forms. There is, however, significant variability in age of onset and the course of disease among types.
The sialidoses are autosomal recessive lysosomal storage disorders resulting from mutations in the NEU1 gene (6p21.3) which lead to an intracellular accumulation of glycoproteins containing sialic acid residues. Both types I and II are caused by mutations in the same gene.
Treatment is focused on symptom management.
This is an anterior corneal dystrophy involving the epithelium and Bowman membrane. Opacities consisting of spots and lines form in the central portion of the anterior cornea creating haziness with relative sparring of the periphery. These can be seen as early as 4-5 years of age but few symptoms occur until the epithelium breaks down causing painful corneal erosions. Visual acuity eventually drops as the corneal haze increases along with increasing irregularity of the epithelial surface.
Ultrastructural studies reveal degenerative changes in all epithelial cells and almost complete Bowman membrane replacement with disoriented collagen fibrils.
A comparative histological study of Reis-B√ºcklers and Thiel-Behnke dystrophies concluded that these are distinct CDB (corneal dystrophy Bowman) disorders and suggested the former be called CDB type I, and the latter CDB type II. Type II is considered unique on the basis of the ‘curly’ fibers seen in the Bowman and subepithelial layers, while type I has bandshaped granular Masson-positive subepithelial deposits and ‘rod-shaped bodies’ resembling granular dystrophy. Type I described here generally leads to greater vision loss than type II.
No systemic disease is associated with Reis-B√ºcklers corneal dystrophy.
This disorder seems to be closely related to the more common Thiel-Behnke dystrophy as the corneal disease is caused in both cases by missense mutations in the TGFBI gene on chromosome 5 (5q31). The mutation in Reis-B√ºcklers results in a p.Arg124Leu amino acid substitution whereas most cases of Thiel-Behnke dystrophy are the result of a p. Arg555Gln substitution. Both disorders are inherited in an autosomal dominant pattern.
Ablation of the diseased cornea can improve vision and provide temporary relief from the erosions.
This disorder, reported so far in a single family, is an anterior corneal dystrophy with onset in the first decade of life. The frequency of epithelial erosions tended to subside during adolescence but visual acuity continued to decline secondary to subepithelial nodular opacities and a generalized haze most dense centrally. No geographic lines are present and cystic changes in the epithelium were absent. Bowman layer and deeper stuctures of the cornea are unaffected. Patients may have 20/30 vision into the fifth decade but after that it may decrease into the 20/400 range. EM revealed accumulations of subepithelial fibrillar material. Light microscopy and immunohistochemistry showed the material to be chondroitin-4-sulfate and dermatan sulfate.
No systemic disease association has been reported.
In the single 3 generation family reported, the pattern of inheritance was consistent with autosomal dominant inheritance. No locus or mutation has been reported.
The usual treatment for acute corneal erosions might be beneficial but other treatments have not been reported. Penetrating keratoplasty and superficial keratectomy have been used on several patients but followup is not available.
Individuals have the onset of recurrent corneal erosions as a result of as yet unknown disease processes. Onset is in the first decade of life (even in the first year of life) often with some subepithelial haze or blebs while denser centrally located opacities develop with time. Erosions often are precipitated by relatively minor trauma and are often difficult to treat, lasting for up to a week. Fortunately, the erosions become less frequent as patients age and may cease altogether by the fifth decade of life.
No systemic disease is associated with ERED.
The few reported families have all had an autosomal dominant pattern of inheritance. So far no locus or molecular defect has been identified.
The clinical features of this condition are found in other corneal dystrophies and it is likely that at least some of the reported cases may have had other unrecognized corneal conditions.
The usual corneal erosion treatment of hypertonic solutions, bandage patching, and lubricating ointments may be helpful for acute erosions. No long term preventative treatment has been found effective. Corneal transplants remain clear centrally although peripheral opacities may reappear within a few years.