Cystinosis

Cystinosis
Other namesCystine storage disease,[1] Abderhalden–Lignac–Kaufmann disease,[2] Abderhalden–Kaufmann–Lignac syndrome
Chemical structure of cystine formed from L-cysteine (under biological conditions)
SpecialtyEndocrinology Edit this on Wikidata

Cystinosis is a lysosomal storage disease characterized by the abnormal accumulation of cystine, the oxidized dimer of the amino acid cysteine.[3] It is a genetic disorder that follows an autosomal recessive inheritance pattern. It is a rare autosomal recessive disorder resulting from accumulation of free cystine in lysosomes, eventually leading to intracellular crystal formation throughout the body. Cystinosis is the most common cause of Fanconi syndrome in the pediatric age group. Fanconi syndrome occurs when the function of cells in renal tubules is impaired, leading to abnormal amounts of carbohydrates and amino acids in the urine, excessive urination, and low blood levels of potassium and phosphates.[citation needed]

Cystinosis was the first documented genetic disease belonging to the group of lysosomal storage disease disorders.[4] Cystinosis is caused by mutations in the CTNS gene that codes for cystinosin, the lysosomal membrane-specific transporter for cystine. Intracellular metabolism of cystine, as it happens with all amino acids, requires its transport across the cell membrane. After degradation of endocytosed protein to cystine within lysosomes, it is normally transported to the cytosol. But if there is a defect in the carrier protein, cystine is accumulated in lysosomes. As cystine is highly insoluble, when its concentration in tissue lysosomes increases, its solubility is immediately exceeded and crystalline precipitates are formed in almost all organs and tissues.[5]

However, the progression of the disease is not related to the presence of crystals in target tissues. Although tissue damage might depend on cystine accumulation, the mechanisms of tissue damage are not fully understood. Increased intracellular cystine profoundly disturbs cellular oxidative metabolism and glutathione status,[6] leading to altered mitochondrial energy metabolism, autophagy, and apoptosis.[7]

Cystinosis is usually treated with cysteamine, which is prescribed to decrease intralysosomal cystine accumulation.[8] However, the discovery of new pathogenic mechanisms and the development of an animal model of the disease may open possibilities for the development of new treatment modalities to improve long-term prognosis.[4]

  1. ^ Cite error: The named reference gen was invoked but never defined (see the help page).
  2. ^ "Abderhalden Kaufmann Lignac syndrome". rarediseases.info.nih.gov. Archived from the original on 15 May 2018. Retrieved 15 May 2018.
  3. ^ A. Gahl, William; Jess G. Thoene; Jerry A. Schneider (2002). "Cystinosis". N Engl J Med. 347 (2): 111–121. doi:10.1056/NEJMra020552. PMID 12110740.
  4. ^ a b Nesterova G, Gahl WA. Cystinosis: the evolution of a treatable disease. Pediatr Nephrol 2012;28:51–9.
  5. ^ Gahl WA, Thoene JG, Schneider JA. Cystinosis. N Engl J Med 2002;347:111-121.
  6. ^ Kumar A, Bachhawat AK. A futile cycle, formed between two ATP-dependent γ-glutamyl cycle enzymes, γ-glutamyl cysteine synthetase and 5-oxoprolinase: the cause of cellular ATP depletion in nephrotic cystinosis?; J Biosci 2010;35:21–25.
  7. ^ Park MA, Thoene JG. Potential role of apoptosis in development of the cystinotic phenotype. Pediatr Nephrol 2005;20:441–446.
  8. ^ Besouw M, Masereeuw R, Van den Heuvel L et al. Cysteamine: an old drug with new potential. Drug Discov Today 2013.