Rare Gastroenterology News

Disease Profile

Cystinosis

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

Infancy

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ICD-10

E72.0

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Cystine diathesis; Cystine disease; Cystine storage disease;

Categories

Congenital and Genetic Diseases; Eye diseases; Kidney and Urinary Diseases;

Summary

Cystinosis is a genetic condition present from birth that leads to the build-up of cystine crystals in the body. This can impact all the organs and tissues, but mainly affects the kidneys and eyes. There are three types of cystinosis based on the age that symptoms start. The most common is the type that starts in infancy. Early symptoms include poor feeding, vomiting, and dehydration. If left untreated, cystinosis leads to kidney and eye damage which gets worse over time. The adult form of cystinosis primarily affects the eyes, causing light sensitivity. Cystinosis is caused by genetic changes (DNA variants) in the CTNS gene and is inherited in an autosomal recessive pattern. It is diagnosed by checking for cystine levels in the blood, by genetic testing, or by an eye examination. Treatment is available using medications that absorb extra cystine from the body. Some people require a kidney transplant.[1][2][3]

Symptoms

The following list includes the most common signs and symptoms in people with cystinosis. These features may be different from person to person. Some people may have more symptoms than others and symptoms can range from mild to severe. This list also does not include every symptom or feature that has been described in this condition.

Symptoms may include:[1][2]

Symptoms usually begin in early infancy with poor growth and difficulty feeding. Symptoms of the intermediate form are similar to the infant form, but they start in later childhood and tend to be milder. The major symptom of the adult-onset form is light sensitivity (photophobia).

Treatment with medications that remove excess cystine can slow down or prevent symptoms. The earlier treatment begins the better the outcome. Without treatment, people with cystinosis may have kidney failure by their early teens.[3][4]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Cause

Cystinosis is caused by genetic changes (DNA variants) in the CTNS gene.[1][2]

Diagnosis

Cystinosis is diagnosed based on a clinical examination, symptoms, and genetic testing to look for DNA variants in the CTNS gene. Other diagnostic testing includes a blood test to look for unusually high levels of cystine and a special exam to look for cystine crystals in the eye.[1][2][3]

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    Cystinosis is treated using daily medication that absorb the excess cystine from the body. Treatment slows down and sometimes eliminates the complications of cystinosis. Other treatments are aimed at managing the symptoms including nutritional support and hormone replacement. Some people need a kidney transplant.[4][5] 

    Specialists that may be involved in the care of someone with cystinosis include:

    • Nephrologist (kidney specialist)
    • Ophthalmologist (eye specialist)
    • Neurologist (nerve specialist)

    FDA-Approved Treatments

    The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

    Medical Terms Other Names
    Learn More:
    HPO ID
    80%-99% of people have these symptoms
    Aminoaciduria
    High urine amino acid levels
    Increased levels of animo acids in urine

    [ more ]

    0003355
    Corneal opacity
    0007957
    Dehydration
    0001944
    Delayed puberty
    Delayed pubertal development
    Delayed pubertal growth
    Pubertal delay

    [ more ]

    0000823
    Failure to thrive
    Faltering weight
    Weight faltering

    [ more ]

    0001508
    Fatigue
    Tired
    Tiredness

    [ more ]

    0012378
    Hypokalemia
    Low blood potassium levels
    0002900
    Hypophosphatemia
    Low blood phosphate level
    0002148
    Hypothyroidism
    Underactive thyroid
    0000821
    Muscle weakness
    Muscular weakness
    0001324
    Myopathy
    Muscle tissue disease
    0003198
    Nephrogenic diabetes insipidus
    0009806
    Nephropathy
    0000112
    Photophobia
    Light hypersensitivity
    Extreme sensitivity of the eyes to light

    [ more ]

    0000613
    Polydipsia
    Extreme thirst
    0001959
    Proteinuria
    High urine protein levels
    Protein in urine

    [ more ]

    0000093
    Renal tubular dysfunction
    Abnormal function of filtrating structures in kidney
    0000124
    Short stature
    Decreased body height
    Small stature

    [ more ]

    0004322
    Stereotypy
    Repetitive movements
    Repetitive or self-injurious behavior

    [ more ]

    0000733
    Type I diabetes mellitus
    Type 1 diabetes
    Type I diabetes

    [ more ]

    0100651
    Vomiting
    Throwing up
    0002013
    30%-79% of people have these symptoms
    Renal insufficiency
    Renal failure
    Renal failure in adulthood

    [ more ]

    0000083
    Retinopathy
    Noninflammatory retina disease
    0000488
    Rickets
    Weak and soft bones
    0002748
    5%-29% of people have these symptoms
    Abnormal pyramidal sign
    0007256
    Cranial nerve paralysis
    0006824
    Dysphasia
    0002357
    Fever
    0001945
    Gait disturbance
    Abnormal gait
    Abnormal walk
    Impaired gait

    [ more ]

    0001288
    Intellectual disability, mild
    Mental retardation, borderline-mild
    Mild and nonprogressive mental retardation
    Mild mental retardation

    [ more ]

    0001256
    Malabsorption
    Intestinal malabsorption
    0002024
    Portal hypertension
    0001409
    Visual impairment
    Impaired vision
    Loss of eyesight
    Poor vision

    [ more ]

    0000505
    1%-4% of people have these symptoms
    Blindness
    0000618
    Cerebral calcification
    Abnormal deposits of calcium in the brain
    0002514
    Diabetes mellitus
    0000819
    Male hypogonadism
    Decreased function of male gonad
    0000026
    Oral-pharyngeal dysphagia
    0200136
    Primary hypothyroidism
    0000832
    Renal Fanconi syndrome
    0001994
    Stage 5 chronic kidney disease
    0003774
    Percent of people who have these symptoms is not available through HPO
    Autosomal recessive inheritance
    0000007
    Cerebral atrophy
    Degeneration of cerebrum
    0002059
    Corneal crystals
    0000531
    Decreased plasma carnitine
    0003234
    Delayed skeletal maturation
    Delayed bone maturation
    Delayed skeletal development

    [ more ]

    0002750
    Dysphagia
    Poor swallowing
    Swallowing difficulties
    Swallowing difficulty

    [ more ]

    0002015
    Elevated intracellular cystine
    0003358
    Episodic metabolic acidosis
    0004911
    Exocrine pancreatic insufficiency
    Inability to properly digest food due to lack of pancreatic digestive enzymes
    0001738
    Failure to thrive in infancy
    Faltering weight in infancy
    Weight faltering in infancy

    [ more ]

    0001531
    Frontal bossing
    0002007
    Generalized aminoaciduria
    0002909
    Genu valgum
    Knock knees
    0002857
    Glycosuria
    Glucose in urine
    0003076
    Growth abnormality
    Abnormal growth
    Growth issue

    [ more ]

    0001507
    Conditions with similar signs and symptoms from Orphanet
    Differential diagnosis includes other diseases causing renal Fanconi syndrome (Lowe syndrome, Dent disease, galactosemia, fructose intolerance, thyrosinemia, mitochondrial nephropathies, Wilson disease, Fanconi-Bickel syndrome, lysinuric protein intolerance, idiopathic Fanconi syndromes, secondary Fanconi syndrome due to drug toxicity or substance abuse, recovery of acute tubulus necrosis), diseases causing phosphaturia and rickets, and proteinuria of unknown etiology.
    Visit the Orphanet disease page for more information.

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Social Networking Websites

      • The Cystinosis Research Foundation provides the Cystinosis Research Foundation Facebook page where people with cystinosis and their families can connect with others worldwide.
      • RareConnect has an online community for patients and families with this condition so they can connect with others and share their experiences living with a rare disease. The project is a joint collaboration between EURORDIS (European Rare Disease Organisation) and NORD (National Organization for Rare Disorders).

        Learn more

        These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

        Where to Start

          In-Depth Information

          • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
          • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
          • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
            Nephropathic cystinosis
            Adult non-nephropathic cystinosis
            Late-onset nephropathic cystinosis
          • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Cystinosis. Click on the link to view a sample search on this topic.

            References

            1. Elmonem MA, Veys KR, Soliman NA, van Dyck M, van den Heuvel LP, Levtchenko E. Cystinosis: a review. Orphanet J Rare Dis. 2016; 11:47. https://pubmed.ncbi.nlm.nih.gov/27102039.
            2. Neserova G, Gahl WA. Cystinosis. GeneReviews. Updated Dec 7, 2017; https://pubmed.ncbi.nlm.nih.gov/20301574.
            3. Veys KR, Elmonem MA, Arcolino FO, van den Heuvel L, Levtchenko E.. Nephropathic cystinosis: an update. Curr Opin Pediatr. 2017; 29(2):168-178. https://pubmed.ncbi.nlm.nih.gov/28107209.
            4. Ariceta G, Giordano V, Santos F. Effects of long-term cysteamine treatment in patients with cystinosis. Pediatr Nephrol. 2019; 34(4):571-578. https://pubmed.ncbi.nlm.nih.gov/29260317.
            5. Nesterova G, Gahl W. Infantile nephropathic cystinosis: Standards of Care. Cystinosis Research Network. June 2012; https://www.cystinosis.org/wp-content/uploads/2019/01/CRN_StandardsofCare_FINAL_1.pdf.
            6. Emma F, Nesterova G, Langman C, Labbé A, Cherqui S et al. Nephropathic cystinosis: an international consensus document. Nephrol Dial Transplant. 2014; 29 Suppl 4(Suppl 4):iv87-iv94. https://pubmed.ncbi.nlm.nih.gov/25165189.

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