Cystinosis - Causes, Symptoms, Diagnosis, and Treatment

What Is Cystinosis?

Cystinosis is a hereditary disorder in which the amino acid called cystine gets accumulated in large amounts in the organs and tissues of the body. The most commonly affected organs in cystinosis are the kidneys, eyes, liver, muscles, and pancreas. It mainly affects infants and causes damage to the kidneys and eyes. The minerals required by the body are excreted in large amounts in the urine, and the kidneys permanently fail to work if the condition is left untreated for a long time.

What Are the Different Types of Cystinosis?

The different types of cystinosis have been described in the table below:

What Causes Cystinosis?

Cystinosis occurs due to a defective protein present in the lysosomal membrane. The lysosomes are present within the cells. They work to break down complex nutrients like proteins and fats into simpler substances so that they can be easily digested by the cells. Under normal conditions, the amino acid cysteine is converted to cystine in the lysosomes. After the cellular digestion is complete, both these substances (cystine and cysteine) move out of the lysosomes. Next, the cystine gets converted to cysteine by glutathione and is sent to the kidneys for excretion. Cystinosis occurs when the proteins that send cystine out of the lysosomes become defective. The mechanism which causes cystinosis has been described below:

1. The lysosome is bounded by the membranes on all sides. A cystinosine lysosomal cystine transporter gene (CTNS) is present on the lysosomal membrane. This gene commands the body to make a protein called cystinosin.

2. The cystinosin protein is present in the lysosomal membrane. It is responsible for the transport of cystine and cysteine out of the lysosomes.

3. In cystinosis, this cystinosine lysosomal cystine transporter gene (CTNS) becomes defective (mutation) and unable to provide instructions to the body regarding cystinosin formation.

4. As a result, cystinosin is missing from the lysosomal membrane, and cystine remains within the lysosomes. Slowly, the cystine starts forming crystals that get deposited in the kidneys, eyes, liver, and pancreas resulting in a condition called cystinosis.

What Are the Signs and Symptoms of Cystinosis?

The signs and symptoms of different types of cystinosis have been described below:

Nephropathic Cystinosis - It is the most severe type and commonly affects infants. The baby does not present with any symptoms in the first six to twelve months. However, the following symptoms are usually noted after twelve months:

1. The growth and development of the baby are delayed.

2. It becomes difficult for the baby to survive because he does not like to eat anything or just wants to have salty and spicy food items.

3. Nausea, vomiting, and fever occur repeatedly.

4. The bowel movements become difficult, resulting in constipation.

5. The child is unable to gain weight.

6. The patient feels thirsty all the time and remains dehydrated.

What Are Some of the Other Symptoms of Nephropathic Cystinosis?

Nephropathic cystinosis affects not only the kidneys but also the other organs. The symptoms are listed below:

1. If the cystine crystals get deposited in the thyroid gland, hypothyroidism occurs because of the deficiency of thyroid hormone. As a result, the growth and maturation of the child get delayed.

2. The eyes become dry because of the inability to produce tears.

3. The males remain infertile because of delayed puberty and reduced testosterone levels. Testosterone is a hormone that is responsible for the growth and maturation of the reproductive organs in men.

4. The children are unable to focus on their studies, experience difficulty in learning, and fail to identify objects by touch.

Intermediate Cystinosis - The signs and symptoms of intermediate cystinosis are similar to the nephropathic one, but they appear later in life. The kidneys are completely damaged and fail to carry out their daily activities. If the condition is left untreated, kidney failure occurs at a young age making it difficult for the person to survive later. The patient has to be on dialysis or undergo a kidney transplant to eliminate the waste products from the body.

Non-nephropathic Cystinosis - It is also known as ocular cystinosis because it affects the eyes mainly. The cystine crystals form in the eyes, and the child develops sensitivity to bright light. It becomes difficult for him to read as the eyes pain in the presence of light resulting in a condition called photophobia.

How Does Nephropathic Cystinosis Affect the Kidneys?

Nephropathic cystinosis affects the kidneys to a large extent, as infants suffering from this disease are most likely to develop Fanconi syndrome. The kidneys are a crucial organ of the urogenital system. They filter the blood, form urine, and maintain the levels of sodium, potassium, calcium, magnesium, and proteins in the body. The kidneys contain tiny filtration units and tubules that allow the waste products to pass and reabsorb the minerals and proteins required by the body. These tubules get damaged in nephropathic cystinosis due to Fanconi syndrome. As a result, the important minerals pass out of the body because of the failure of the kidneys to absorb them, causing the deficiency of these minerals. The following symptoms are seen in Fanconi syndrome:

• The urine is produced in excess, so the patient passes urine frequently (polyuria).

• A large amount of water is lost in the urine, so the patient feels thirsty all the time (polydipsia).

• Dehydration and vomiting accompanied by fever are commonly seen.

Fanconi syndrome also presents with a compilation that has been described below:

Hypophosphatemic Rickets- The kidneys have failed to work because of Fanconi syndrome and are unable to reabsorb minerals and electrolytes from the urine. A condition known as hypophosphatemic rickets occurs when the kidneys cannot reabsorb phosphates from the urine. As a result, the body derives phosphorus from the bones and makes them weak. Once the bones become weak, they start paining, making it difficult for the child to walk.

What Tests Are Done to Diagnose Cystinosis?

The following tests are usually done to diagnose cystinosis:

1. Blood Tests - It is done to check the levels of electrolytes like sodium, potassium, magnesium, and calcium in the blood and polymorphonuclear leukocytes. If their levels are above or below their normal range, kidney disease can be suspected.

2. Urine Test - In this test, the patient collects urine in a container. The urine sample is then examined in the laboratory under the microscope. If the kidneys have failed or cannot filter the blood, the minerals, electrolytes, proteins, and other important substances are present in excess in the urine.

3. Prenatal Diagnosis - In this test, a small amount of amniotic fluid is taken from the body and examined under the microscope. In cystinosis, the cells present in the amniotic fluid show the presence of cystine. This helps to diagnose cystinosis even before the baby is born. Amniotic fluid surrounds the baby within the womb.

4. Slit-lamp Test - The slit-lamp test is done to detect the crystals in the eyes and the surrounding area. The doctor checks the eyes with the help of a microscope and a slit lamp. It helps to check if any other abnormality is present in the eyes due to cystinosis.

5. Imaging Tests - The imaging tests, including computed tomography (CT) and magnetic resonance imaging (MRI) scans, are done in children presenting with learning difficulties. It provides an idea about the condition of the brain because it is the primary learning center.

What Is the Treatment of Cystinosis?

The treatment of cystinosis depends upon the symptoms the patient presents with. Nephropathic cystinosis was considered a life-threatening disorder previously because there were no drugs available to target it. As medical science advanced further and research was done, the drugs that reduce the cystine levels in the body were discovered. The treatment of cystinosis has been described below:

• Cysteamine Drugs - Cysteamine is an agent that reduces the levels of cystine in the cells. It also saves the kidneys from getting damaged permanently. As a result, the patient is not required to undergo a kidney transplant at an early age. The drug that is used as a cysteamine agent is delayed-release Cysteamine bitartrate. The patient must start taking the drug as soon as the condition is diagnosed and continue the drug throughout life. It is usually taken by mouth (orally), but the disadvantage is that it fails to remove the crystals from the eyes as it is unable to penetrate them. Cysteamine eye drops were introduced later to solve the eye problems associated with cystinosis.

• Management of Dehydration - Dehydration or the loss of fluids from the body occurs in Fanconi syndrome. The child must be administered a sufficient amount of fluids and electrolytes, mainly sodium, potassium, magnesium, and calcium, to overcome their loss from the body. The fluids should be continued until the electrolyte levels of the body return to normal.

• Indomethacin - Indomethacin belongs to the category of nonsteroidal anti-inflammatory drugs (NSAID) and is used to slow down the filtration process in the kidneys. The effects of the drug should be carefully monitored because it can lead to serious complications if consumed in excess.

• Growth Hormone Therapy - The growth hormone is injected into the body of young children to improve their growth.

• Thyroid Hormone Therapy - L-thyroxine is usually administered to stimulate the thyroid gland to produce thyroid hormone in children suffering from hypothyroidism.

What Are the Complications of Cystinosis?

The following complications occur if cystinosis is left untreated for long:

1. The muscles of the hands, arms, and shoulders become weak due to the deposition of cystine (myopathy). If the cystine gets deposited in the throat muscles, it becomes difficult for the child to eat.

2. It becomes difficult for the patient to digest food because the enzymes that break down food and help in digestion are missing.

3. The risk of diabetes increases because of the damage to the pancreas. The insulin produced by the pancreas maintains blood glucose levels. If the pancreas is not working, insulin deficiency occurs, resulting in diabetes.

4. Heart diseases and a rise in blood pressure occur if the cystine gets deposited in the heart and the blood vessels.

Conclusion:

Cystinosis occurs when cystine gets deposited in the organs and tissues of the body. It mainly occurs when the gene responsible for regulating cystine transport is defective. The most severe complication of cystinosis is Fanconi syndrome. It affects the kidneys to the extent that they stop working, and the patient loses a large number of fluids and electrolytes in the urine. Cystinosis was thought to be a life-threatening condition earlier, but with the discovery of new drugs, the condition is managed easily. The parents must notify the signs and symptoms in the child and consult the doctor immediately because timely diagnosis and treatment help to save the kidneys and other organs from getting damaged.