It has a reported incidence of 1:192,000 1. Cystinosis is typically diagnosed in infancy.
Cystinosis typically presents with failure to thrive and a Fanconi syndrome in early infancy. Progressive multi-organ involvement develops over the first few decades of life.
- renal manifestations
- photophobia, blepharospasm from corneal involvement
- distal vacuolar myopathy presenting as progressive distal muscle wasting and weakness
- central nervous system
- hypotonia, speech delay, motor impairment, cognitive dysfunction have been described 5
- primary hypothyroidism 3
- pancreatic exocrine failure causing clinical diabetes mellitus by the age of 18 years in 50% of patients 4
- primary hypogonadism in males
- hypopigmentation, coarsened facial features, impaired sweating have been described 6
There are three main clinical phenotypes:
- infantile form (95%)
- most severe with early-onset renal failure
- juvenile-onset form (5%)
- slower onset to renal failure and milder degrees of Fanconi syndrome
- adult form (case reports)
- corneal involvement with renal sparing
Cystinosis is caused by a mutation of the CTNS gene, which is inherited in an autosomal recessive inheritance pattern. This gene encodes cystinosin, a transporter that carries cystine from lysosomes into the cytoplasm. A defect in the CTNS gene causes an accumulation of cystine in lysosomes, leading to cystine crystallization and resultant lysosomal dysfunction 2. Lysosomal dysfunction in cystinosis manifests across a variety of organ systems, most prominently in the renal system.
Imaging features are non-specific and may include:
Treatment and prognosis
The mainstay of treatment is cystine-depleting therapy with cysteamine 7. With modern medical therapy, life expectancy can extend past 50 years.
History and etymology
Initially described by Swiss biochemist Emil Abderhalden (1877-1950) 8.
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- 2. Galina Nesterova, William A. Gahl. Cystinosis: the evolution of a treatable disease. (2013) Pediatric Nephrology. 28 (1): 51. doi:10.1007/s00467-012-2242-5 - Pubmed
- 3. Chan AM, Lynch MJ, Bailey JD, Ezrin C, Fraser D. Hypothyroidism in cystinosis. A clinical, endocrinologic and histologic study involving sixteen patients with cystinosis. (1970) The American journal of medicine. 48 (6): 678-92. Pubmed
- 4. Filler G, Amendt P, von Bredow MA, Rohde W, Ehrich JH. Slowly deteriorating insulin secretion and C-peptide production characterizes diabetes mellitus in infantile cystinosis. (1998) European journal of pediatrics. 157 (9): 738-42. Pubmed
- 5. Fink JK, Brouwers P, Barton N, Malekzadeh MH, Sato S, Hill S, Cohen WE, Fivush B, Gahl WA. Neurologic complications in long-standing nephropathic cystinosis. (1989) Archives of neurology. 46 (5): 543-8. Pubmed
- 6. Guillet G, Sassolas B, Fromentoux S, Gobin E, Leroy JP. Skin storage of cystine and premature skin ageing in cystinosis. (1998) Lancet (London, England). 352 (9138): 1444-5. Pubmed
- 7. Emma F, Nesterova G, Langman C, Labbé A, Cherqui S, Goodyer P, Janssen MC, Greco M, Topaloglu R, Elenberg E, Dohil R, Trauner D, Antignac C, Cochat P, Kaskel F, Servais A, Wühl E, Niaudet P, Van't Hoff W, Gahl W, Levtchenko E. Nephropathic cystinosis: an international consensus document. (2014) Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 29 Suppl 4: iv87-94. doi:10.1093/ndt/gfu090 - Pubmed
- 8. Familiäre Cystindiathese. (2018) Hoppe-Seyler´s Zeitschrift für physiologische Chemie. 38 (5-6): 557. doi:10.1515/bchm2.1903.38.5-6.557