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Nephropathic Cystinosis

 Nephropathic Cystinosis



Overview

Nephropathic cystinosis, also known as infantile or early-onset cystinosis, is a severe, inherited disorder where cystine, an amino acid, builds up in the body's lysosomes (cellular compartments that break down waste). This buildup primarily affects the kidneys, leading to a condition called Fanconi syndrome, and if left untreated, can progress to end-stage renal disease. It's caused by mutations in the CTNS gene, which is responsible for producing the cystinosis protein, a lysosomal transporter. 

Symptoms

Kidney Dysfunction:

Fanconi Syndrome: The kidneys lose essential substances like sodium, potassium, phosphate, and glucose in the urine, leading to electrolyte imbalances. 

Polyuria and Polydipsia: Excessive urination and thirst due to the kidneys' inability to concentrate urine. 

Dehydration: Can result from fluid loss due to excessive urination. 

Growth Impairment: Children with nephropathic cystinosis often experience failure to thrive and delayed puberty. 

Gastrointestinal Issues: Vomiting, diarrhea, and feeding difficulties can occur due to electrolyte imbalances and kidney dysfunction. 

Muscle Weakness: Muscle weakness and neuromuscular issues can also develop. 

Photophobia: Sensitivity to light due to cystine crystal deposits in the cornea, often developing later in childhood. 

Metabolic Acidosis: Can occur due to the kidneys' inability to regulate acid-base balance. 

Progression of Symptoms:

Infants may present with failure to thrive, polyuria, polydipsia, and electrolyte imbalances.

By ages 3-4, photophobia often develops.

Without treatment, renal failure can occur by ages 10-12.

Neurological symptoms, such as tremor and hypotonia, can also develop. 

Causes

Genetic Basis:

Cystinosis is an autosomal recessive disorder, meaning an individual needs to inherit two copies of the mutated CTNS gene (one from each parent) to develop the condition. 

Cystinosis Deficiency:

The CTNS gene provides instructions for making the cystinosis protein. In cystinosis, mutations in this gene impair cystinosis's ability to transport cystine out of lysosomes. 

Lysosomal Accumulation:

Cystine, an amino acid, accumulates within the lysosomes due to the defective cystinosin. This buildup forms crystals that damage cells and tissues, particularly in the kidneys, eyes, and other organs. 

Organ Damage:

The accumulation of cystine crystals leads to a range of complications, including Fanconi syndrome (a kidney disorder) and eventually end-stage renal disease in nephropathic cystinosis. 

Geographic Variations:

While the phenotype (clinical presentation) of cystinosis is generally the same, different pathogenic mutations in the CTNS gene can be found in various geographic regions. 

Diagnosis

Clinical Evaluation:

A thorough assessment of the patient's medical history, symptoms (including growth impairment, kidney dysfunction, and photophobia), and physical examination is the first step. 

Laboratory Tests:

White Blood Cell Cystine Measurement: Measuring cystine levels in white blood cells is a primary diagnostic test. Elevated levels confirm the presence of cystinosis. 

Urinalysis: Urine tests can detect the excess loss of minerals, nutrients, electrolytes, and amino acids, which are characteristic of Fanconi syndrome, a common complication of nephropathic cystinosis. 

Other blood tests and kidney function tests: These are used to assess the overall health of the kidneys and other organs. 

Genetic Testing:

Analysis of the CTNS gene, which is responsible for cystinosis, can identify specific mutations and confirm the diagnosis. 

Eye Examination:

An ophthalmologist can use a slit lamp to examine the cornea for cystine crystals, which are a hallmark of the disease. 

Kidney Biopsy:

In some cases, a kidney biopsy may be performed to assess the extent of cystine crystal accumulation and tissue damage. 

Prenatal Testing:

If there is a family history of cystinosis, prenatal testing (amniocentesis or chorionic villus sampling) may be offered to assess the risk of the fetus developing the condition. 

Treatment

Cystagon™ (immediate-release) and Procyclin™ (delayed-release):

These are the two forms of cysteamine available. Cystagon™ requires frequent dosing (every 6 hours), while Procyclin™ is a delayed-release version that can be taken every 12 hours, according to Cleveland Clinic. 

Cysteamine Eye Drops:

Cystaran™ and Cyst drops™ are cysteamine eye drops used to dissolve corneal cystine crystals and relieve light sensitivity. 

Goal of Treatment:

Cysteamine therapy aims to lower cystine levels in cells, slowing the progression of kidney damage and improving overall outcomes. Early and consistent treatment is crucial for maximizing its benefits. 

Management of Fanconi Syndrome:

Fluid and Electrolyte Management:

Cystinosis can cause the kidneys to lose essential fluids and electrolytes, requiring careful monitoring and replacement. 

Nutritional Adjustments:

Nutritional support, including supplements and potentially growth hormones, may be needed to address deficiencies caused by Fanconi syndrome. 

Type of Doctor Department :  A nephrologist 


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