Cystinosis
Etiology and Pathogenesis [1]Impaired efflux of cystine across lysosomal membranes results in intralysosomal accumulation of free cystine. Key Symptom Images
Image Credits: Cystine crystal deposits courtesy of Kleta et al Mayo Clin Proc.
Clinical Description and Progression/Prognosis [1]Cystine accumulation results in cystine crystals in the cornea, conjunctiva, bone marrow, lymph nodes, leukocytes, and internal organs. Three variants of cystinosis have been identified:  Infantile (nephropathic) - Leads to Fanconi syndrome and renal insufficiency in the 1st decade. Growth retardation, vomiting, fever, vitamin D-resistant rickets, polyuria, dehydration, and metabolic acidosis are usually evident by 4-6 months. Photophobia is usually demonstrable within the first years of life; retinal degeneration may appear even earlier. Death due to uremia or intercurrent infection usually occurs by age 10. Juvenile - Ocular and renal manifestations are milder than in the infantile form and become evident by the 2nd decade. Not usually fatal. Adult (benign) - Involves cystine deposits in the cornea but not the kidney. Photophobia, headache, and burning or itching of the eyes are the major indications. Not fatal.
Inheritance pattern: autosomal recessive Incidence: 1 in 192,000 live births [2] Diagnosis: urinary loss of nutrients; cystine measurement in leukocytes; typical cystine crystals on slit lamp examination of cornea [3] Conditions with similar presentations: Wilson disease, the oculocerebrorenal syndrome of Lowe, galactosemia, glycogen storage disease type I, tyrosinemia type I [3] Management: no disease-specific treatment available Other medical care:[4] symptom management. Renal disease treated as other forms of chronic renal failure. The free thiol cysteamine slows progression of renal dysfunction, improves growth, and dissolves corneal cystine crystals. However, gradual kidney dysfunction continues. Kidney transplantation has proven successful; transplant patients have not developed the functional abnormalities of cystinosis in transplanted organs.
Infantile and juvenile forms only Fanconi Syndrome (generalized proximal tubular dysfunction): Episodes of vomiting, dehydration, weakness, and unexplained fever Anorexia, constipation Polydipsia and polyuria Failure to thrive and grow Rickets Cystinosis - chronic renal failure (CRF) leading to end-stage renal failure Refractile polychromatic crystals deposited in the conjunctiva, cornea, sclera, and choroid Peripheral retinopathy (beginning at 5 weeks of age) Hypo-pigmented fundi with fine to coarse spotty pigmentation Photophobia Back to categories
1. www.seychelles.net/smdj/95issue/short_reports.htm
2. Meikle PJ, Hopwood JJ, Clague AE, Carey WF. Prevalence of Lysosomal Storage Disorders. JAMA. 1999; 281: 249-254.
3. Kleta, Robert, MD, PhD; Gahl, William A, MD, PhD. “Cystinosis.” www.genetests.org. Updated 6 June 2003.
4. www.cystinosisfoundation.org/Documents/CystinosisNEJMarticle.pdf |
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