Cystinosis

What causes it?

An amino acid called cystine accumulates in cells, causing damage to organs such as the kidneys, eyes, muscles, pancreas and brain.

Cystine is made by cells during natural metabolism and is normally carried out of the cell, but in cystinosis it can't be. Instead, it builds up to 100 times the normal level, forming crystals that eventually destroy the cell.

Who's affected?

Cystinosis follows a pattern of autosomal recessive inheritance. This means both parents carry a faulty gene but don't have the disease, because they also each have a normal gene to compensate. If they both pass the recessive cystinosis gene to their child, the disease will develop.

Although cystinosis can seem to appear out of the blue, there may be a history of illness in the family and sometimes unexplained early deaths in childhood.

What are the symptoms?

There are three types of cystinosis: infantile, late-onset and benign.

In infantile cystinosis, also known as nephropathic cystinosis, the baby may appear normal at birth with problems arising in the first year or two.

Symptoms include:

• Failure to thrive
• Poor appetite
• Excessive thirst and urine production
• Rickets (due to a lack of phosphate)
• Dehydration, which combined with a problem in sweat production often leads to recurrent fevers

These symptoms are caused by damage to two parts of the kidneys' filtering units: the tubules and glomeruli. Tubular damage causes renal Fanconi syndrome - a type of renal tubular acidosis where nutrients, salts and minerals are lost in the urine. This occurs in very young children and needs urgent treatment. More long-term damage occurs to the glomeruli.

Without treatment, the kidneys eventually fail and the child needs dialysis or a transplant.

Other symptoms include:

• Accumulation of crystals in the eyes, leading to damage to the retina and loss of sight - photophobia (pain or dislike of bright light) may be a problem
• Raised cystine levels in the white blood cells
• Poor growth
• Muscle wasting
• Damage to the pancreas, which can cause diabetes
• Hypothyroidism

In late-onset cystinosis, also called intermediate cystinosis, symptoms can appear from about the age of two to the mid-20s, but usually start around the age of 12 or 13.

The symptoms are the same as those in infantile cystinosis but may not be as severe and full Fanconi syndrome may not develop. However, kidney (renal) failure does progress and within a few years a transplant is needed.

There's no kidney damage in benign cystinosis, also called non-nephropathic cystinosis. The condition is often discovered by chance during an eye test, when crystalline opacities are found in the cornea and conjunctiva (the surface layers of the eye). However, the retina isn't damaged.

Other symptoms may include mild photophobia that begins in adult life. Crystals are also deposited in the bone marrow and white blood cells, but may cause no symptoms.

What's the treatment?

Treatment aims to combat the symptoms of cystinosis.

The excessive fluid and nutrient loss associated with Fanconi's syndrome means children require adequate amounts of water, minerals, salt and bicarbonate. Most need to drink solutions of sodium and potassium citrate.

Many also require vitamin D and phosphate supplements to prevent rickets. Hypothyroidism may need treatment with thyroxine, while diabetes will require insulin. In addition, some children are given growth hormones.

The drug cysteamine (a type of aminothiol therapy) helps to reduce the accumulation of cystine in the cells, lowering the amount of damage done to tissues. This treatment may prevent or delay kidney failure and improve growth. Eye drops containing cysteamine can help to reduce damage to the cornea.

Couples with children who have cystinosis may wish to take steps to avoid the condition in future children. Techniques such as chorionic villus sampling (CVS) and amniocentesis can be used during the early stages of pregnancy to see if the unborn child is affected.