sampling has been reported in ML II for prenatal diagnosis.

MANAGEMENT Both PK and lamellar keratoplasty (LK) have been associated with generally poor results, probably because resurfacing is impaired by the abnormal epithelial cells. Allograft limbal stem cell transplantation may be an option. Bone marrow transplantation has been reported.

Disorders of Amino Acid Metabolism

Table 11-2 summarizes the ocular and systemic findings in disorders of amino acid metabolism.

Table 11-2

Cystinosis

Cystinosis is a rare autosomal recessive metabolic disorder characterized by the accumulation of the amino acid cystine within lysosomes. It affects 3.5 infants per 1 million births. Cystinosis has been mapped to band 17p13; the defective gene is CTNS.

PATHOGENESIS A defect in transport across the lysosomal membrane leads to intracellular accumulation of cystine.

CLINICAL FINDINGS Cystinosis is categorized based on the age at diagnosis and severity of symptoms. Nephropathic cystinosis is divided into infantile (classic) and intermediate (juvenile or adolescent) forms. Dwarfism and progressive renal dysfunction are prominent in infantile cystinosis and less severe in the juvenile disease. Life expectancy is normal in non-nephropathic cystinosis (formerly called adult cystinosis). All 3 types are characterized by the deposition of fine polychromatic cystine crystals in the conjunctiva, cornea, and other parts of the eye. The crystals are densest in the peripheral cornea (Fig 11-3); but they are seen throughout the anterior stroma, even within the central cornea, and can be seen in the trabecular meshwork with gonioscopy. Cystinosis patients are often photophobic. The crystals, however, usually do not affect vision; they can recur following PK.

Figure 11-3 Cystinosis. Refractile polychromatic crystals are clustered in the peripheral cornea.

LABORATORY EVALUATION Cystine crystals may be seen in conjunctival biopsy, blood leukocytes, or bone marrow.

MANAGEMENT Topical cysteamine drops reduce the density of the crystals and diminish corneal pain, possibly by reducing the frequency of corneal erosions. Cysteamine is thought to react with intracellular cystine, forming a cysteine-cysteamine disulfide that resembles lysine and is transported through the lysosome by the normal lysine transport system. Posterior manifestations such as pigmentary retinopathy and optic nerve involvement may be treated with oral cysteamine, which may also prevent or delay other manifestations of the disease, including death.

Tsilou E, Zhou M, Gahl W, Sieving PC, Chan CC. Ophthalmic manifestations and histopathology of infantile nephropathic cystinosis: report of a case and review of the literature. Surv Ophthalmol. 2007;52(1):97–105.

Tyrosinemia

Richner-Hanhart syndrome (tyrosinemia type II) is characterized by hyperkeratotic lesions of the palms, soles, and elbows, as well as eventual cognitive impairment.

PATHOGENESIS This autosomal recessive disorder results from defective tyrosine aminotransferase, which leads to excess tyrosine in the blood and urine. The elevated tyrosine level likely has a direct action on lysosomal membranes, leading to enzyme release. The gene defect is located at 16q22.1- q22.3.