Ophthalmic Manifestations and Histopathology of Infantile Nephropathic Cystinosis: Report of a Case and Review of the Literature

Abstract

Cystinosis is a rare autosomal recessive metabolic disorder characterized by the intracellular accumulation of cystine, the disulfide of the amino acid cysteine, in many organs and tissues. Infantile nephropathic cystinosis is the most severe phenotype. Corneal crystal accumulation and pigmentary retinopathy were originally the most commonly described ophthalmic manifestations, but successful kidney transplantation significantly changed the natural history of the disease. As cystinosis patients now live longer, long-term complications in extrarenal tissues including the eye, have become apparent. A case of an adult patient with infantile nephropathic cystinosis is reported. He presented with many long-term ocular complications of cystinosis. After 4 years of follow-up, the patient died from sepsis. Pathology of the phthisical eyes demonstrated numerous electron transparent polygonal spaces, bounded by single membrane, in corneal cells, retinal pigment epithelial cells, and even choroidal endothelial cells. The ophthalmic manifestations and pathology of infantile nephropathic cystinosis are discussed and reviewed in light of the current report and other cases in the literature.

Efficacy of topical cysteamine in nephropathic cystinosis

“…The most commonly encountered ocular symptoms of corneal cystinosis include photophobia, foreign body sensation and pain 3 4. In our study, 18 (56%) patients had photophobia at presentation.…”

“…Nephropathic cystinosis is divided into infantile (classic) and intermediate (juvenile-onset or adolescent) types. Non-nephropathic cystinosis was formerly called benign or adult type cystinosis but is now termed ocular cystinosis 3. Nephropathic or classic infantile cystinosis is the most severe phenotype.…”

“…Nephropathic or classic infantile cystinosis is the most severe phenotype. If untreated, it inevitably leads to terminal renal failure in the first decade of life 2 3. Early manifestations include Fanconi's tubular syndrome, which develops in 95% of patients as early as 6–12 months of life.…”

Antioxidant Effect of Cysteamine in Brain Cortex of Young Rats

“…This cystine-depleting drug is therapeutically important in the treatment of cystinosis, a rare autosomal recessive metabolic disorder caused by mutations of the lysosomal cystine carrier cystinosin encoded by the CTNS gene, responsible for cystine exodus from the lysosomes [6]. As a result of deficient or absent cystine transporter, the disulfide amino acid accumulates within lysosomes and crystallizes in many tissues and organs, including the kidney and nervous system [7,8]. In the most common type of cystinosis, nephropathic or infantile cystinosis, renal tubular Fanconi syndrome occurs at 6-12 months of age and progresses, if untreated, to terminal renal failure before the age of 10 [9].…”

Inherited metabolic disorders involving the eye: a clinico-biochemical perspective

“…The pathognomonic ocular manifestation of cystinosis is the deposition of distinctive iridescent crystals in the cornea. 22 Ocular symptoms include glare, photophobia, decreased corneal sensation, and mild decrease in vision.…”