Marfan Syndrome

Marfan syndrome is a common autosomal dominant disorder associated with disorders of the eye (ectopia lentis), heart (dilation of the aortic root and aneurysms of the aorta), and skeletal system (arachnodactyly, pectus excavatum, and kyphoscoliosis). It maps to band 15q21.1 (fibrillin gene).

PATHOGENESIS Fibrillin and glycoprotein make up the microfibrillar system of the extracellular matrix. Fibrillin is found in corneal basement membrane, zonular fibers of the lens and capsule, and sclera.

CLINICAL FINDINGS Defects in fibrillin synthesis lead to thinning of the sclera (blue sclera), subluxation of the lens, and flattening of the cornea. BCSC Section 11, Lens and Cataract, discusses and illustrates the lens subluxation caused by Marfan syndrome. Open-angle glaucoma and cataract occur at a higher rate and an earlier age than in the normal population. Megalocornea and keratoconus are uncommon, but excessive flattening (35 D range) occurs in up to 20% of patients.

MANAGEMENT Cardiac evaluation should be completed, as premature mortality is associated with aortic complications. Treatment of lens subluxation may require the use of advanced cataract surgery techniques such as capsular tension rings or scleral fixation; in severe cases of subluxation, a pars plana approach may be a better option to safely remove the lens.

Disorders of Nucleotide Metabolism

Gout

Disorders of purine metabolism cause hyperuricemia (increased uric acid). Gout results from deposition of urate crystals in the joints or kidney.

PATHOGENESIS Hyperuricemia may be familial, as a result of an enzyme deficiency (eg, hypoxanthine phosphoribosyltransferase in Lesch-Nyhan syndrome). More commonly, it is polygenic or secondary to obesity, cytotoxic chemotherapy, myeloproliferative disease, diuretic therapy, or excessive alcohol consumption.

CLINICAL FINDINGS Acute inflammation of the sclera, episclera, or conjunctiva can occur. Fine corneal epithelial and stromal deposits may appear in the absence of inflammation. See Table 11-4 for differential diagnosis of corneal deposits. An orange-brown band keratopathy or a typical whitish band keratopathy is seen in rare cases.

LABORATORY EVALUATION Serum uric acid level is typically elevated. However, in urate keratopathy, the uric acid level may be normal in the presence of keratopathy if there is no concurrent inflammation.

MANAGEMENT Acute treatment is with indomethacin, colchicine, or phenylbutazone; long-term reduction in uric acid levels should be pursued with medications such as allopurinol. Superficial deposits can be removed mechanically with scraping or keratectomy.

Porphyria

The porphyrias are a group of disorders characterized by excess production and excretion of porphyrins, pigments involved in the synthesis of heme.