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Cystinosis

MedGen UID:
1384792
Concept ID:
C4316899
Disease or Syndrome
Synonyms: Cystine diathesis; Cystine disease; Cystine storage disease; Cystinoses
SNOMED CT: Cystinosis (190681003); Cystine disease (190681003); Cystine storage disease (190681003); Cystine diathesis (190681003)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Related gene: CTNS
 
Monarch Initiative: MONDO:0016239
OMIM®: 219800
Orphanet: ORPHA213

Disease characteristics

Excerpted from the GeneReview: Cystinosis
Cystinosis comprises three allelic phenotypes: Nephropathic cystinosis in untreated children is characterized by renal Fanconi syndrome, poor growth, hypophosphatemic/calcipenic rickets, impaired glomerular function resulting in complete glomerular failure, and accumulation of cystine in almost all cells, leading to cellular dysfunction with tissue and organ impairment. The typical untreated child has short stature, rickets, and photophobia. Failure to thrive is generally noticed after approximately age six months; signs of renal tubular Fanconi syndrome (polyuria, polydipsia, dehydration, and acidosis) appear as early as age six months; corneal crystals can be present before age one year and are always present after age 16 months. Prior to the use of renal transplantation and cystine-depleting therapy, the life span in nephropathic cystinosis was no longer than ten years. With these interventions, affected individuals can survive at least into the mid-forties or fifties with satisfactory quality of life. Intermediate cystinosis is characterized by all the typical manifestations of nephropathic cystinosis, but onset is at a later age. Renal glomerular failure occurs in all untreated affected individuals, usually between ages 15 and 25 years. The non-nephropathic (ocular) form of cystinosis is characterized clinically only by photophobia resulting from corneal cystine crystal accumulation. [from GeneReviews]
Authors:
Galina Nesterova  |  William A Gahl   view full author information

Additional description

From MedlinePlus Genetics
Cystinosis is a condition characterized by accumulation of the amino acid cystine (a building block of proteins) within cells. Excess cystine damages cells and often forms crystals that can build up and cause problems in many organs and tissues. The kidneys and eyes are especially vulnerable to damage; the muscles, thyroid, pancreas, and testes may also be affected.

There are three distinct types of cystinosis. In order of decreasing severity, they are nephropathic cystinosis, intermediate cystinosis, and non-nephropathic or ocular cystinosis.

Nephropathic cystinosis begins in infancy, causing poor growth and a particular type of kidney damage (renal Fanconi syndrome) in which certain molecules that should be reabsorbed into the bloodstream are instead eliminated in the urine. The kidney problems lead to the loss of important minerals, salts, fluids, and many other nutrients. The loss of nutrients impairs growth and may result in soft, bowed bones (hypophosphatemic rickets), especially in the legs. The nutrient imbalances in the body lead to increased urination, thirst, dehydration, and abnormally acidic blood (acidosis). By about the age of 2, cystine crystals may be present in the clear covering of the eye (cornea). The buildup of these crystals in the eye causes pain and an increased sensitivity to light (photophobia). Untreated children will experience complete kidney failure by about the age of 10. Other signs and symptoms that may occur in untreated people, especially after adolescence, include muscle deterioration, blindness, inability to swallow, diabetes, thyroid and nervous system problems, and an inability to father children (infertility) in affected men.

The signs and symptoms of intermediate cystinosis are the same as nephropathic cystinosis, but they occur at a later age. Intermediate cystinosis typically becomes apparent in affected individuals in adolescence. Malfunctioning kidneys and corneal crystals are the main initial features of this disorder. If intermediate cystinosis is left untreated, complete kidney failure will occur, but usually not until the late teens to mid-twenties.

People with non-nephropathic or ocular cystinosis typically experience photophobia due to cystine crystals in the cornea, but usually do not develop kidney malfunction or most of the other signs and symptoms of cystinosis. Due to the absence of severe symptoms, the age at which this form of cystinosis is diagnosed varies widely.  https://medlineplus.gov/genetics/condition/cystinosis

Professional guidelines

PubMed

Hohenfellner K, Elenberg E, Ariceta G, Nesterova G, Soliman NA, Topaloglu R
Cells 2022 Mar 25;11(7) doi: 10.3390/cells11071109. PMID: 35406673Free PMC Article
Haffner D, Leifheit-Nestler M, Grund A, Schnabel D
Pediatr Nephrol 2022 Oct;37(10):2289-2302. Epub 2022 Mar 29 doi: 10.1007/s00467-022-05505-5. PMID: 35352187Free PMC Article
Jamalpoor A, Othman A, Levtchenko EN, Masereeuw R, Janssen MJ
Trends Mol Med 2021 Jul;27(7):673-686. Epub 2021 May 8 doi: 10.1016/j.molmed.2021.04.004. PMID: 33975805

Recent clinical studies

Etiology

Hohenfellner K, Zerell K, Haffner D
Klin Monbl Augenheilkd 2023 Mar;240(3):251-259. Epub 2023 Mar 28 doi: 10.1055/a-2022-8522. PMID: 36977426
Veys KR, Elmonem MA, Arcolino FO, van den Heuvel L, Levtchenko E
Curr Opin Pediatr 2017 Apr;29(2):168-178. doi: 10.1097/MOP.0000000000000462. PMID: 28107209
Ariceta G, Camacho JA, Fernández-Obispo M, Fernández-Polo A, Gamez J, García-Villoria J, Lara Monteczuma E, Leyes P, Martín-Begué N, Oppenheimer F, Perelló M, Morell GP, Torra R, Santandreu AV, Güell A; Grupo T-CiS.bcn
Nefrologia 2015;35(3):304-21. doi: 10.1016/j.nefroe.2015.06.010. PMID: 26523297
Klintworth GK
Orphanet J Rare Dis 2009 Feb 23;4:7. doi: 10.1186/1750-1172-4-7. PMID: 19236704Free PMC Article
Mancini GM, Havelaar AC, Verheijen FW
J Inherit Metab Dis 2000 May;23(3):278-92. doi: 10.1023/a:1005640214408. PMID: 10863944

Diagnosis

Hohenfellner K, Zerell K, Haffner D
Klin Monbl Augenheilkd 2023 Mar;240(3):251-259. Epub 2023 Mar 28 doi: 10.1055/a-2022-8522. PMID: 36977426
Albuquerque ALB, Dos Santos Borges R, Conegundes AF, Dos Santos EE, Fu FMM, Araujo CT, Vaz de Castro PAS, Simões E Silva AC
World J Pediatr 2023 Jul;19(7):619-634. Epub 2023 Feb 2 doi: 10.1007/s12519-023-00685-y. PMID: 36729281
Foreman JW
Pediatr Clin North Am 2019 Feb;66(1):159-167. doi: 10.1016/j.pcl.2018.09.002. PMID: 30454741
Elmonem MA, Veys KR, Soliman NA, van Dyck M, van den Heuvel LP, Levtchenko E
Orphanet J Rare Dis 2016 Apr 22;11:47. doi: 10.1186/s13023-016-0426-y. PMID: 27102039Free PMC Article
Veys KR, Besouw MT, Pinxten AM, Dyck MV, Casteels I, Levtchenko EN
Acta Clin Belg 2016 Jun;71(3):131-7. doi: 10.1179/2295333714Y.0000000113. PMID: 25560059

Therapy

Hohenfellner K, Zerell K, Haffner D
Klin Monbl Augenheilkd 2023 Mar;240(3):251-259. Epub 2023 Mar 28 doi: 10.1055/a-2022-8522. PMID: 36977426
Haffner D, Leifheit-Nestler M, Grund A, Schnabel D
Pediatr Nephrol 2022 Oct;37(10):2289-2302. Epub 2022 Mar 29 doi: 10.1007/s00467-022-05505-5. PMID: 35352187Free PMC Article
Ames EG, Thoene JG
Cells 2022 Feb 15;11(4) doi: 10.3390/cells11040670. PMID: 35203319Free PMC Article
Veys KR, Elmonem MA, Arcolino FO, van den Heuvel L, Levtchenko E
Curr Opin Pediatr 2017 Apr;29(2):168-178. doi: 10.1097/MOP.0000000000000462. PMID: 28107209
Veys KR, Besouw MT, Pinxten AM, Dyck MV, Casteels I, Levtchenko EN
Acta Clin Belg 2016 Jun;71(3):131-7. doi: 10.1179/2295333714Y.0000000113. PMID: 25560059

Prognosis

Albuquerque ALB, Dos Santos Borges R, Conegundes AF, Dos Santos EE, Fu FMM, Araujo CT, Vaz de Castro PAS, Simões E Silva AC
World J Pediatr 2023 Jul;19(7):619-634. Epub 2023 Feb 2 doi: 10.1007/s12519-023-00685-y. PMID: 36729281
Emma F, Montini G, Pennesi M, Peruzzi L, Verrina E, Goffredo BM, Canalini F, Cassiman D, Rossi S, Levtchenko E
Cells 2022 Jun 4;11(11) doi: 10.3390/cells11111839. PMID: 35681534Free PMC Article
Veys KR, Elmonem MA, Arcolino FO, van den Heuvel L, Levtchenko E
Curr Opin Pediatr 2017 Apr;29(2):168-178. doi: 10.1097/MOP.0000000000000462. PMID: 28107209
Veys KR, Besouw MT, Pinxten AM, Dyck MV, Casteels I, Levtchenko EN
Acta Clin Belg 2016 Jun;71(3):131-7. doi: 10.1179/2295333714Y.0000000113. PMID: 25560059
Klintworth GK
Orphanet J Rare Dis 2009 Feb 23;4:7. doi: 10.1186/1750-1172-4-7. PMID: 19236704Free PMC Article

Clinical prediction guides

Vashist N, Deshpande AA, Kanakaraj A, Ravichandran R, Bachhawat AK
J Biosci 2023;48 PMID: 38018544
Müller S, Kluck R, Jagodzinski C, Brügelmann M, Hohenfellner K, Büscher A, Kemper MJ, Fröde K, Oh J, Billing H, Thumfart J, Weber LT, Acham-Roschitz B, Arbeiter K, Tönshoff B, Hagenberg M, Pavičić L, Haffner D, Zivicnjak M
Pediatr Nephrol 2023 Dec;38(12):3989-3999. Epub 2023 Jul 7 doi: 10.1007/s00467-023-06058-x. PMID: 37415042Free PMC Article
Servais A, Boisgontier J, Saitovitch A, Hummel A, Boddaert N
Cells 2022 Feb 15;11(4) doi: 10.3390/cells11040682. PMID: 35203331Free PMC Article
Haffner D, Leifheit-Nestler M, Alioli C, Bacchetta J
Cells 2022 Jan 5;11(1) doi: 10.3390/cells11010170. PMID: 35011732Free PMC Article
De Laey JJ
Bull Soc Belge Ophtalmol 1993;249:11-22. PMID: 7952338

Recent systematic reviews

Kaur S, Sarma P, Kaur H, Prajapat M, Shekhar N, Bhattacharyya J, Kaur H, Kumar S, Medhi B, Ram J, Das D, Avti P, Prakash A, Singh R, Bhattacharyya A
Am J Ophthalmol 2021 Mar;223:275-285. Epub 2020 Sep 2 doi: 10.1016/j.ajo.2020.07.052. PMID: 32888903
Kasimer RN, Langman CB
Pediatr Nephrol 2021 Feb;36(2):223-236. Epub 2020 Feb 3 doi: 10.1007/s00467-020-04487-6. PMID: 32016627
Medic G, van der Weijden M, Karabis A, Hemels M
Curr Med Res Opin 2017 Nov;33(11):2065-2076. Epub 2017 Aug 3 doi: 10.1080/03007995.2017.1354288. PMID: 28692321

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