Metabolic diseases

Metabolic diseases, also known as inborn errors of metabolism, are known to cause corneal opacity. The majority of metabolic diseases are inherited in an AR fashion and are due to dysfunctional lysosomal enzymes (lysosomal storage disease). The poorly or nonfunctioning enzymes allow the collection of metabolic debris in the end organ where that enzyme is being used and often includes the cornea. It is important to understand that the patient with a metabolic disease due to an inborn error of metabolism may be born with a clear cornea and develop clouding over time. The two main classes of inborn errors of metabolism include errors of carbohydrate metabolism (mucopolysaccharidosis) and lipid metabolism (mucolipidosis).

Mucopolysaccharidosis

ETIOLOGY

Not every mucopolysaccharidosis (MPS) causes corneal clouding. The most commonly associated MPS that have corneal findings include MPS I-H (Hurler’s syndrome), MPS I-S (Scheie’s syndrome), MPS II (Hunter’s syndrome), MPS IV A and B (Morquio’s syndrome), and MPS VI A and B (Maroteaux–Lamy syndrome). Glycosaminoglycans (GAGs) are very important in maintaining the structure of the cornea. Keratin sulfate and chondroitin sulfate serve as the backbone for the extracellular matrix of the cornea keeping a constant interfibrillar distance.50 If the distance is altered the clarity of the cornea is reduced. Heparin sulfate and other GAGs are also expressed in the epithelial layer of the cornea and likely play a role in corneal wound healing.51 With the disruption in GAG metabolism, lysosomal storage products collect, causing a loss of clarity in the cornea as well as symptoms associated with deposition in other target organs.

DIAGNOSIS

Diagnosis is based upon the clinical manifestations of the disease along with laboratory confirmation of the genetic/enzymatic defect involved.

MANAGEMENT/TREATMENT AND PROGNOSIS

The current treatment for many of the mucopolysaccharidoses is bone marrow transplantation to replace hematopoietic stem cells. With early treatment many of the signs of the storage diseases can be minimized including corneal clouding.52 Enzyme replacement is also an option for these patients; however, the ocular findings may not regress and may continue to worsen.53 Gene replacement therapy shows promise in treating MPS. Most studies are currently in animal models, but with time this may become a treatment option in humans.54

The prognosis for retention of good vision is based upon the clarity of the central cornea and the involvement of other structures of the eye such as the retina or optic nerve. The overall prognosis for these patients is dependent on involvement of other vital organ systems that may occur in each individual disorder.