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{{Infobox medical condition (new)
{{SI}}
{{Infobox medical condition
| name            = Cystinosis
| name            = Cystinosis
| synonyms        = Cystine storage disease<ref name=gen/>
| image          = [[File:Cystine-skeletal.png|alt=Cystine molecule structure]]
| image          = Cystine-skeletal.png
| caption        = Structure of cystine
| caption        = Chemical structure of [[cystine]] formed from L-cysteine (under biological conditions)
| field          = [[Nephrology]], [[Genetics]]
| pronounce      =  
| symptoms        = [[Fanconi syndrome]], [[growth retardation]], [[photophobia]], [[renal failure]]
| field          =  
| complications  = [[Kidney failure]], [[hypothyroidism]], [[diabetes mellitus]], [[muscle wasting]]
| symptoms        =  
| onset          = Infancy
| complications  =  
| duration        = Lifelong
| onset          =  
| types          = [[Nephropathic cystinosis]], [[Intermediate cystinosis]], [[Ocular cystinosis]]
| duration        =  
| causes          = Mutations in the [[CTNS]] gene
| types          =  
| risks          = [[Autosomal recessive]] inheritance
| causes          =  
| diagnosis      = [[Genetic testing]], [[corneal cystine crystal]] examination
| risks          =  
| differential    = [[Fanconi syndrome]], [[cystinuria]], [[other metabolic disorders]]
| diagnosis      =  
| treatment      = [[Cysteamine]], [[kidney transplantation]], [[symptomatic treatment]]
| differential    =  
| medication      = [[Cysteamine]]
| prevention      =
| prognosis      = Variable, depends on treatment
| treatment      =  
| frequency      = 1 in 100,000 to 200,000 live births
| medication      =  
| prognosis      =  
| frequency      =  
| deaths          =
}}
}}
 
Cystinosis
<youtube>
Cystinosis is a rare, inherited metabolic disorder characterized by the accumulation of the amino acid cystine within lysosomes, leading to cellular damage. This condition primarily affects the kidneys and eyes, but can also impact other organs and tissues.
title='''{{PAGENAME}}'''
==Pathophysiology==
movie_url=http://www.youtube.com/v/f4cfUnVufEE
Cystinosis is caused by mutations in the [[CTNS gene]], which encodes the protein cystinosin. Cystinosin is responsible for transporting cystine out of lysosomes. When this transport is impaired, cystine accumulates, forming crystals that can cause cellular dysfunction and damage.
&rel=1
==Types of Cystinosis==
embed_source_url=http://www.youtube.com/v/f4cfUnVufEE
Cystinosis is classified into three main types based on the age of onset and severity of symptoms:
&rel=1
===Nephropathic Cystinosis===
wrap = yes
This is the most common and severe form, typically presenting in infancy. It is characterized by renal tubular Fanconi syndrome, leading to excessive loss of water, sodium, potassium, and other substances in the urine.
width=750
===Intermediate Cystinosis===
height=600
Also known as juvenile or adolescent cystinosis, this form presents later in childhood or adolescence. It is less severe than nephropathic cystinosis but can still lead to significant kidney damage over time.
</youtube>
===Ocular Cystinosis===
 
This form primarily affects the eyes, causing photophobia and corneal crystal deposits. It usually presents in adulthood and does not typically involve kidney dysfunction.
'''Cystinosis''' is a [[lysosomal storage disease]] characterized by the abnormal accumulation of the [[amino acid]] [[cystine]]. It is a [[genetic disorder]] that follows an [[dominance relationship|autosomal recessive]] [[inheritance]] pattern. It is a rare autosomal recessive disorder resulting from accumulation of free cystine in [[lysosome]]s, 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 tubule]]s is impaired, leading to abnormal amounts of [[carbohydrate]]s and amino acids in the [[urine]], excessive urination, and low blood levels of [[potassium]] and [[phosphate]]s.
==Clinical Manifestations==
 
===Renal Symptoms===
Cystinosis was the first documented genetic disease belonging to the group of lysosomal storage disease disorders. Cystinosis is caused by mutations in the ''[[CTNS (gene)|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 [[endocytosis|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.
- '''Fanconi Syndrome''': Characterized by polyuria, polydipsia, and growth retardation due to renal tubular dysfunction.
 
- '''Chronic Kidney Disease''': Progressive renal impairment leading to end-stage renal disease if untreated.
 
===Ocular Symptoms===
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,
- '''Photophobia''': Sensitivity to light due to corneal cystine crystal deposits.
 
- '''Corneal Crystals''': Visible deposits in the cornea that can be detected by slit-lamp examination.
Cystinosis is usually treated with [[cysteamine]], which is prescribed to decrease intralysosomal cystine accumulation.<ref>Besouw M, Masereeuw R, Van den Heuvel L et al. Cysteamine: an old drug with new potential. Drug Discov Today 2013.
===Other Symptoms===
 
- '''Hypothyroidism''': Due to cystine accumulation in the thyroid gland.
==Symptoms==
- '''Diabetes Mellitus''': Resulting from pancreatic involvement.
There (are) three distinct types of cystinosis each with slightly different symptoms: nephropathic cystinosis, intermediate cystinosis, and non-nephropathic or ocular cystinosis. Infants affected by nephropathic cystinosis initially exhibit poor growth and particular [[kidney]] problems (sometimes called renal [[Fanconi syndrome]]).
- '''Muscle Weakness''': Due to cystine accumulation in muscle tissue.
 
The kidney problems lead to the loss of important minerals, salts, fluids, and other nutrients. The loss of nutrients not only impairs growth, but 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]]).  
 
[[File:Nephropathic cystenosis NHGRI-79209.jpg|right|thumb|Slit-lamp photographs of three-year-old patient with nephropathic cystinosis before (left) and after (right) cysteamine eyedrop therapy. The drops dissolve the crystals in the cornea.]]
 
By about age two, cystine crystals may also be present in the [[cornea]]. The buildup of these crystals in the eye causes an increased sensitivity to light ([[photophobia]]). Without treatment, children with cystinosis are likely to experience complete kidney failure by about age ten. With treatment this may be delayed into the patients teens or 20s. Other signs and symptoms that may occur in patients include muscle deterioration, blindness, inability to swallow, impaired sweating, decreased hair and skin pigmentation, [[diabetes]], and [[thyroid]] and [[nervous system]] problems.
 
The signs and symptoms of intermediate cystinosis are the same as nephropathic cystinosis, but they occur at a later age. Intermediate cystinosis typically begins to affect individuals around age twelve to fifteen. 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 do not usually experience growth impairment or kidney malfunction. The only symptom is photophobia due to cystine crystals in the cornea.
 
===Crystal morphology and identification===
Cystine crystals are hexagonal in shape and are colorless. They are not found often in alkaline urine due to their high solubility. The colorless crystals can be difficult to distinguish from uric acid crystals which are also hexagonal. Under polarized examination, the crystals are birefringent with a polarization color interference.
==Genetics==
[[Image:autorecessive.svg|thumb|right|Cystinosis has an autosomal recessive pattern of inheritance.]]
 
Cystinosis occurs due to a mutation in the gene [[CTNS (gene)|CTNS]], located on [[chromosome 17]], which codes for cystinosin, the lysosomal cystine transporter. Symptoms are first seen at about 3 to 18 months of age with profound [[polyuria]] (excessive urination), followed by poor growth, [[photophobia]], and ultimately [[renal failure|kidney failure]] by age 6 years in the nephropathic form.
 
All forms of cystinosis (nephropathic, juvenile and ocular) are [[autosomal recessive]], which means that the trait is located on an autosomal gene, and an individual who inherits two copies of the gene – one from both parents – will have the disorder. There is a 25% risk of having a child with the disorder, when both parents are carriers of an autosomal recessive trait.
 
Cystinosis affects approximately 1 in 100,000 to 200,000 newborns.
 
==Diagnosis==
==Diagnosis==
Cystinosis is a rare genetic disorder that causes an accumulation of the [[amino acid]] [[cystine]] within cells, forming crystals that can build up and damage the cells. These crystals negatively affect many systems in the body, especially the kidneys and eyes.
Diagnosis of cystinosis is based on clinical presentation, family history, and laboratory tests. Measurement of cystine levels in leukocytes is a key diagnostic test. Genetic testing can confirm mutations in the CTNS gene.
 
The accumulation is caused by abnormal transport of cystine from [[lysosome]]s, resulting in a massive intra-lysosomal cystine accumulation in tissues. Via an as yet unknown mechanism, lysosomal cystine appears to amplify and alter [[apoptosis]] in such a way that cells die inappropriately, leading to loss of renal epithelial cells. This results in renal [[Fanconi syndrome]], and similar loss in other tissues can account for the short stature, retinopathy, and other features of the disease.
 
Definitive diagnosis and treatment monitoring are most often performed through measurement of white blood cell [[cystine]] level using [[tandem mass spectrometry]].
 
===Types===
* {{OMIM|219800}} – Infantile nephropathic
* {{OMIM|219900}} – Adolescent nephropathic
* {{OMIM|219750}} – Adult nonnephropathic
 
==Treatment==
==Treatment==
Cystinosis is normally treated with [[cysteamine]], which is available in capsules and in eye drops. People with cystinosis are also often given [[sodium citrate]] to treat the blood acidosis, as well as potassium and phosphorus supplements as well as others. If the kidneys become significantly impaired or fail, then treatment must be begun to ensure continued survival, up to and including [[renal transplantation]].
===Cysteamine Therapy===
 
Cysteamine is the primary treatment for cystinosis. It reduces cystine accumulation by converting cystine into cysteine and cysteine-cysteamine mixed disulfide, which can exit the lysosome.
==Cystinotic==
===Supportive Care===
The related adjective "cystinotic" indicates "relating to, or afflicted with, cystinosis".
- '''Renal Replacement Therapy''': Dialysis or kidney transplantation for end-stage renal disease.
* {{NLM|cystinosis}}
- '''Electrolyte Replacement''': To manage Fanconi syndrome.
*[https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=ctns GeneReviews/NCBI/NIH/UW entry on Cystinosis]
- '''Ocular Drops''': Cysteamine eye drops to reduce corneal crystal deposits.
{{Amino acid metabolic pathology}}
==Prognosis==
 
With early diagnosis and treatment, individuals with cystinosis can have improved outcomes. However, untreated cystinosis can lead to significant morbidity and mortality due to renal failure and other complications.
[[Category:Autosomal recessive disorders]]
==Gallery==
[[Category:Amino acid metabolism disorders]]
<gallery>
[[Category:Lysosomal storage diseases]]
File:Nephropathic cystenosis NHGRI-79209.jpg|Cystinosis
File:autorecessive.svg|Cystinosis
</gallery>
==See Also==
- [[Lysosomal storage disease]]
- [[Fanconi syndrome]]
- [[End-stage renal disease]]
[[Category:Genetic disorders]]
[[Category:Metabolic disorders]]
[[Category:Rare diseases]]
[[Category:Rare diseases]]
{{rarediseases}}

Latest revision as of 13:42, 5 April 2025

Editor-In-Chief: Prab R Tumpati, MD
Obesity, Sleep & Internal medicine
Founder, WikiMD Wellnesspedia &
W8MD medical weight loss NYC and sleep center NYC

Cystinosis
Cystine molecule structure
Synonyms N/A
Pronounce N/A
Specialty N/A
Symptoms Fanconi syndrome, growth retardation, photophobia, renal failure
Complications Kidney failure, hypothyroidism, diabetes mellitus, muscle wasting
Onset Infancy
Duration Lifelong
Types Nephropathic cystinosis, Intermediate cystinosis, Ocular cystinosis
Causes Mutations in the CTNS gene
Risks Autosomal recessive inheritance
Diagnosis Genetic testing, corneal cystine crystal examination
Differential diagnosis Fanconi syndrome, cystinuria, other metabolic disorders
Prevention N/A
Treatment Cysteamine, kidney transplantation, symptomatic treatment
Medication Cysteamine
Prognosis Variable, depends on treatment
Frequency 1 in 100,000 to 200,000 live births
Deaths N/A


Cystinosis Cystinosis is a rare, inherited metabolic disorder characterized by the accumulation of the amino acid cystine within lysosomes, leading to cellular damage. This condition primarily affects the kidneys and eyes, but can also impact other organs and tissues.

Pathophysiology[edit]

Cystinosis is caused by mutations in the CTNS gene, which encodes the protein cystinosin. Cystinosin is responsible for transporting cystine out of lysosomes. When this transport is impaired, cystine accumulates, forming crystals that can cause cellular dysfunction and damage.

Types of Cystinosis[edit]

Cystinosis is classified into three main types based on the age of onset and severity of symptoms:

Nephropathic Cystinosis[edit]

This is the most common and severe form, typically presenting in infancy. It is characterized by renal tubular Fanconi syndrome, leading to excessive loss of water, sodium, potassium, and other substances in the urine.

Intermediate Cystinosis[edit]

Also known as juvenile or adolescent cystinosis, this form presents later in childhood or adolescence. It is less severe than nephropathic cystinosis but can still lead to significant kidney damage over time.

Ocular Cystinosis[edit]

This form primarily affects the eyes, causing photophobia and corneal crystal deposits. It usually presents in adulthood and does not typically involve kidney dysfunction.

Clinical Manifestations[edit]

Renal Symptoms[edit]

- Fanconi Syndrome: Characterized by polyuria, polydipsia, and growth retardation due to renal tubular dysfunction. - Chronic Kidney Disease: Progressive renal impairment leading to end-stage renal disease if untreated.

Ocular Symptoms[edit]

- Photophobia: Sensitivity to light due to corneal cystine crystal deposits. - Corneal Crystals: Visible deposits in the cornea that can be detected by slit-lamp examination.

Other Symptoms[edit]

- Hypothyroidism: Due to cystine accumulation in the thyroid gland. - Diabetes Mellitus: Resulting from pancreatic involvement. - Muscle Weakness: Due to cystine accumulation in muscle tissue.

Diagnosis[edit]

Diagnosis of cystinosis is based on clinical presentation, family history, and laboratory tests. Measurement of cystine levels in leukocytes is a key diagnostic test. Genetic testing can confirm mutations in the CTNS gene.

Treatment[edit]

Cysteamine Therapy[edit]

Cysteamine is the primary treatment for cystinosis. It reduces cystine accumulation by converting cystine into cysteine and cysteine-cysteamine mixed disulfide, which can exit the lysosome.

Supportive Care[edit]

- Renal Replacement Therapy: Dialysis or kidney transplantation for end-stage renal disease. - Electrolyte Replacement: To manage Fanconi syndrome. - Ocular Drops: Cysteamine eye drops to reduce corneal crystal deposits.

Prognosis[edit]

With early diagnosis and treatment, individuals with cystinosis can have improved outcomes. However, untreated cystinosis can lead to significant morbidity and mortality due to renal failure and other complications.

Gallery[edit]

  • Cystinosis
    Cystinosis
  • Cystinosis
    Cystinosis

See Also[edit]

- Lysosomal storage disease - Fanconi syndrome - End-stage renal disease

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